Bridging the Gap: A Literature Review of Advancements in Obesity and Diabetes Mellitus Management

Abstract

This literature review explores advancements in obesity and diabetes mellitus diagnosis and treatment, highlighting recent innovations that promise more personalized and effective healthcare interventions. For obesity diagnosis, traditional methods like body mass index (BMI) calculations are now complemented by bioelectrical impedance analysis (BIA) and dual-energy X-ray absorptiometry (DXA) scans, with emerging biomarkers from “omics” technologies. Diabetes diagnosis has advanced with standard hemoglobin A1c (HbA1c) testing supplemented by novel measures such as advanced glycation end products (AGEs) and autoantibodies, alongside the use of artificial intelligence to enhance diagnostic accuracy. Treatment options for obesity are expanding beyond traditional methods. Minimally invasive bariatric surgeries, endoscopic procedures, fecal microbiota transplants (FMTs), and pharmaceuticals like GLP-1 receptor agonists (semaglutide, tirzepatide) show promising results. Cognitive behavioral therapy (CBT) and prescription digital therapeutics (PDTs) are also valuable tools for weight management. Diabetes treatment is also undergoing a transformation. Ultra-long-acting insulins and innovative oral insulin delivery methods are on the horizon. SGLT2 inhibitors and GLP-1 receptor agonists are proving to be effective medications for blood sugar control. Continuous glucose monitoring (CGM) systems and closed-loop insulin delivery are revolutionizing diabetes management, while stem cell therapy holds promise for the future. By integrating advanced diagnostic tools with personalized treatment plans, obesity and diabetes care are entering a new era. This personalized approach empowers patients and paves the way for improved health outcomes and a better quality of life.

1. Introduction

The rise in obesity and diabetes is a growing concern in our society today, presenting substantial obstacles to healthcare systems across the globe. The escalating, pandemic-like spread of obesity and diabetes is creating a colossal hurdle for public health worldwide. In the United States, as of 2024, approximately 31.9% of adults live with obesity [1]. The total number of people living with diabetes in the US was estimated to be 37.3 million in 2024 [2]. In Europe, obesity has shown a significant increase over the past years, and approximately 60% of adults were diagnosed with obesity [3,4]. The prevalence of diabetes comes second after the Americas region, where approximately 31.6 million adults were diagnosed with diabetes in 2024 [5].

Globally, the situation is equally concerning. According to the World Health Organization (WHO), in 2022, an estimated 2.5 billion adults were overweight, with over 890 million classified as obese [6]. This staggering statistic translates to one in eight people worldwide living with obesity, a figure that has more than doubled since 1990. Even more alarming is the rise in childhood obesity, with over 37 million children under 5 and 390 million children and adolescents aged 5–19 now overweight or obese [6]. These trends, documented in the latest Global Burden of Disease Study 2019 [7], signify a global health crisis demanding immediate attention.

The detrimental effects of obesity extend far beyond weight gain. Obesity is a chronic, complex disease defined by excessive fat accumulation that disrupts normal metabolic function and significantly increases the risk of numerous health complications [7]. Individuals with obesity are at a greater risk of developing type 2 diabetes (T2D), heart disease, certain cancers, and musculoskeletal problems. Obesity can also negatively impact the quality of life, affecting mobility, sleep, and overall well-being [8,9,10].

A strong link exists between obesity and T2D. Excess body fat, particularly visceral fat, disrupts insulin signaling and glucose metabolism, ultimately leading to hyperglycemia, the hallmark of diabetes [11]. The presence of obesity significantly increases the risk of developing T2D, with estimates suggesting that 80–90% of individuals with T2D are overweight or obese [12]. Therefore, effectively managing both obesity and T2D is crucial to mitigating this global health crisis.

The economic burden associated with this global health crisis is significant. A 2022 study by the World Obesity Federation highlighted the substantial economic impacts of overweight and obesity across 161 countries [13]. These combined factors underscore the urgent need for effective strategies to prevent and manage obesity and T2D.

This literature review will systematically examine advancements in the management of obesity and T2D, encompassing the entire spectrum from diagnosis to treatment. We will begin by exploring the evolving landscape of diagnostic tools, highlighting the development of more efficient and accurate methods for identifying both conditions. Subsequently, we will explore the current state of treatment, focusing on both traditional and cutting-edge approaches for weight management and glycemic control in diabetes.

The aim of this literature review is to examine advancements in the management of obesity and diabetes, covering the entire spectrum from diagnosis to treatment. It highlights the development of more efficient and accurate diagnostic methods, explores both traditional and cutting-edge treatment approaches for weight management and glycemic control, and underscores the importance of a comprehensive approach integrating lifestyle modifications with pharmacological and interventional treatments. Additionally, it analyzes the growing role of technology in disease management and patient empowerment, providing a comprehensive understanding of effective strategies to diagnose, treat, and ultimately prevent these prevalent conditions.

2. Materials and Methods

This literature review employed a systematic approach to identify and analyze relevant research on advancements in obesity and diabetes management. Here is a breakdown of the key steps involved:

2.1. Search Strategy

Databases: A comprehensive search was conducted across various academic databases, including PubMed, ScienceDirect, Scopus, Web of Science, Google Scholar, and clinicaltrials.gov, for articles published between January 2010 and July 2024.

Keywords: A combination of Medical Subject Headings terms and relevant keywords was used to ensure a focused search. Examples might include obesity, diabetes, diagnosis, treatment, management, lifestyle modifications, pharmacological interventions, technology, and prevention. Boolean operators (AND, OR, NOT) were employed to refine the search and identify the most pertinent studies.

2.2. Inclusion and Exclusion Criteria

Inclusion Criteria: Studies were selected based on their relevance to the research question, focusing on advancements in diagnosing, treating, and managing obesity and diabetes. Studies evaluating interventions, novel diagnostic tools, or technological advancements in these areas were prioritized.

Exclusion Criteria: Studies not directly related to the research question, such as those focusing solely on the etiology of obesity or diabetes, or studies published before the designated date range (January 2010), were excluded. Additionally, studies with methodological limitations or those not published in peer-reviewed journals, or those not providing access to a full text, have been excluded based on quality assessment.

2.3. Selection Process

After conducting the initial search, retrieved articles were screened for duplicates, then by relevance (connected papers), and ultimately by title and abstract to identify potentially relevant studies. Subsequently, full-text articles of shortlisted studies were critically evaluated based on the inclusion and exclusion criteria. This evaluation involved assessing the study design, methodology, findings, and overall contribution to the field.

2.4. Data Extraction and Synthesis

Extracted data from the included studies were systematically organized and categorized based on the themes and topics relevant to the review question. This might involve information on diagnostic tools, treatment approaches, technological advancements, or findings on the effectiveness of various interventions.

The extracted data were then synthesized to provide a comprehensive overview of the current state of knowledge on advancements in obesity and diabetes management.

The search and study selection process is presented in Figure 1.

3. Diagnostic Advancements

3.1. Obesity Diagnostics

While body mass index (BMI) has long been the cornerstone of diagnosing obesity, its limitations are well documented. BMI is a simple calculation based on weight and height, but it does not differentiate between muscle mass and fat, potentially misclassifying individuals with a high proportion of muscle as obese. This highlights the need for more sophisticated diagnostic tools. Recent advancements are offering a more nuanced picture of body composition, paving the way for a more personalized approach to obesity diagnosis [14].

Technological progress: Bioelectrical impedance analysis (BIA) is a well-established, non-invasive technique for obtaining insights into body composition, particularly fluid distribution, lean muscle mass, and body fat percentage. BIA devices send a low-level electrical current through the body, measuring the resistance encountered by different tissues. Muscle tissue conducts electricity more readily than fat, allowing BIA to estimate body fat percentage. Studies have shown BIA to be a relatively quick and non-invasive method for assessing body composition in clinical settings [15,16]. The BIA device demonstrated superior diagnostic capabilities, as evidenced by a higher area under the curve (AUC ≥ 0.94) compared to BMI (AUC 0.89), according to an ROC analysis [17]. Still, studies that have tested BIA devices in comparison to other methods have found that BIA underestimates body fat measurement compared with dual-energy X-ray absorptiometry (DXA), for example, so it does not yet have enough evidence to be considered an interchangeable method of assessing adiposity [18], especially in people for whom these devices have not been developed and approved, indicating that BIA could be a method with limited concordance and validity compared to DXA [19].

However, BIA accuracy can be influenced by hydration levels and requires careful interpretation by trained professionals [20]; as such, the forthcoming investigations have to address these issues more deeply.

Dual-energy X-ray absorptiometry (DXA) scans utilize two different X-ray energies to precisely measure bone mineral density, lean muscle mass, and fat mass throughout the body. DXA scans offer a more detailed and comprehensive assessment of body composition compared to BIA [21]. While DXA scans are highly accurate, they are typically more expensive and time consuming than BIA, limiting their widespread use in primary care settings [19,22].

Beyond these established techniques, the field is actively exploring the potential of novel biomarkers in blood tests for identifying individuals at risk of obesity-related complications. Emerging research suggests that specific blood markers may correlate with increased visceral fat accumulation, a major health concern associated with obesity.

Biomarkers: The field of obesity diagnosis has seen significant advancements with the introduction of biomarkers. Biomarkers have provided a more nuanced understanding of obesity, going beyond traditional measures like BMI and waist circumference [23,24]. Recent research has increasingly relied on new technologies to identify mechanisms in the development of obesity using various “omics” platforms. These include genomics, transcriptomics, proteomics, metabolomics, and lipidomics, which have led to the identification of genetic and epigenetic biomarkers that translate into changes in the transcriptome, proteome, and metabolome [25]. These biomarkers could serve as targets for obesity prevention. In the era of “precision medicine”, there is an increasing interest in novel biomarkers such as adipokines, cytokines, metabolites, and microRNAs implicated in obesity [26]. In the context of the development of modern therapies, some of these biomarkers, such as glucagon-like peptide-1 (GLP-1), monocyte chemoattractant protein-1 (MCP-1), glucose-dependent insulinotropic peptide (GIP), and insulin-like growth factor-binding protein 7 (IGFBP-7), have already shown promising results in clinical trials [27]. Notably, the dysregulation of GLP-1 secretion, frequently observed in obesity, has been linked to diminished levels of GLP-1 and compromised satiety signaling, highlighting its involvement in this condition and emphasizing its potential role as an important biomarker for early diagnostics and therapeutic intervention in metabolic disorders [28].

MCP-1 signaling has been directly linked to the development of obesity, highlighting its significant role in the condition [27,29]. Additionally, obesity is associated with elevated levels of GIP and IGFBP-7, which further underscores the complex metabolic alterations observed in obese individuals [29,30]. These biomarkers present promising targets for a more accurate and earlier diagnosis of obesity, paving the way for tailored therapeutic interventions and improved, personalized prevention. The discovery and integration of these biomarkers with machine learning can lead to the development of predictive tools, feature extraction methods, and a comprehensive evaluation of related factors.

A summary of obesity diagnosis is presented in presented in Figure 2.

In conclusion, advancements in diagnostic tools like BIA, and DXA scans, and the exploration of novel blood-based biomarkers are moving the field beyond the limitations of BMI. These emerging techniques offer a more accurate and personalized approach to diagnosing obesity, allowing for earlier intervention and improved health outcomes for individuals struggling with this chronic condition.

3.2. Diabetes Diagnostics

Just as the field of obesity diagnosis is undergoing a revolution, so too is the approach to diagnosing diabetes. Traditionally, diagnosing diabetes has relied heavily on measuring blood sugar levels, primarily through fasting blood sugar (FBS), hemoglobin A1c (HbA1c), and the oral glucose tolerance test (OGTT). However, these methods, while effective, have limitations. They may miss individuals with prediabetes, and factors like stress or recent meals can influence results, leading to potential misdiagnosis.

This is where exciting advancements in diagnostic tools are emerging, offering a more comprehensive and personalized approach to identifying diabetes risk and the disease itself. Here is a look at some promising new methods:

Advanced Glycation End Products (AGEs): When sugars bond with proteins or fats in the body, they form harmful molecules called AGEs. These accumulate over time, damaging tissues and contributing to various complications associated with diabetes, including neuropathy, nephropathy, and retinopathy [31,32,33]. Research suggests that high levels of AGEs may serve as a marker for diabetes risk, even before blood sugar levels become significantly elevated. Measuring AGEs offers a potential window of opportunity for early intervention and preventative strategies to slow down AGE formation and mitigate future complications [31,32].

Autoantibodies: In type 1 diabetes (T1D), the immune system mistakenly produces antibodies that attack insulin-producing beta cells in the pancreas. Identifying specific autoantibodies, such as antibodies to glutamic acid decarboxylase (anti-GAD) and anti-insulin antibodies, can indicate a predisposition to T1D, particularly in children and young adults [34,35]. Early detection through autoantibody testing allows for closer monitoring and potentially the implementation of therapies that delay or prevent the autoimmune destruction of beta cells.

Genetic Testing: While not yet a definitive diagnostic tool, genetic testing is revealing a growing number of gene variations associated with increased susceptibility to type 2 diabetes. Identifying these genetic risk factors can help healthcare professionals personalize preventative strategies such as dietary modifications and increased physical activity for individuals with a higher genetic predisposition [36,37]. Additionally, understanding the specific genetic landscape of an individual’s diabetes can inform treatment decisions in the future, potentially leading to more targeted therapies.

Artificial Intelligence (AI) and Machine Learning (ML): AI and ML are being increasingly used in the diagnosis of diabetes [38,39]. These technologies can analyze large amounts of data to identify patterns and trends that may not be apparent to human clinicians. They have already been applied to automate the screening of diabetes, detect macrovascular and microvascular complications, and enable multiomic phenotyping for personalized prevention and therapy recommendations [40]. The summary of obesity diagnosis is presented in presented in Figure 3.

The integration of these novel diagnostic tools alongside traditional methods holds immense promise for the future of diabetes diagnosis. By providing a more nuanced picture of an individual’s risk and disease state, these advancements can lead to earlier detection, improved disease management, and potentially a reduction in diabetes-related complications.

4. Treatment Advancements

4.1. Obesity Treatments

For decades, the fight against obesity has centered on lifestyle modifications, emphasizing healthy eating habits and regular physical activity. While these remain the foundation of weight management, the field of obesity treatment is undergoing a renaissance, offering a more comprehensive and multifaceted approach.

Minimally Invasive Procedures: The field of bariatric surgery has undergone a remarkable transformation, moving away from the historically invasive procedures that relied on large abdominal incisions [41,42]. This shift toward minimally invasive surgery (MIS) is fueled by a multitude of advantages. MIS offers patients significant improvements in their postoperative experience, including less pain, minimized scarring, and a shorter hospital stay, leading to a faster return to daily life [37,42]. Additionally, MIS often utilizes specialized laparoscopic instruments and robotics, which can enhance a surgeon’s dexterity and control during the procedure [43].

Furthermore, the landscape of bariatric procedures themselves is constantly evolving. Established procedures like sleeve gastrectomy are being refined, while entirely new approaches like the single-anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) are emerging. After almost 16 years of accumulated experience with SADI-S, this procedure has been intensively studied in terms of its long-term impact on obesity and metabolic diseases, with recent studies still providing evidence of its significant efficacy both in maintaining a low weight [44] and offering significant decreases in blood pressure values, lipid profiles, and uric acid levels [45].

These advancements hold promise for even greater weight loss success and improved management of obesity-related comorbidities [46,47]. However, it should also be mentioned that possible deficiencies in various nutrients and oligoelements following SADI-S surgery are often overlooked. A systematic review of 12 studies involving 581 patients who underwent a SADI-S procedure (217 males and 364 females) observed that selenium, zinc, and iron were the prevalent minerals with deficiencies in a significant number of cases (up to 50% of reported cases), followed by vitamin A deficiency in up to 53% of patients and protein deficiency in up to 34% of patients [48]. These main nutrient deficiencies after SADI-S were also recently reported by Hu et al. [45].

However, there was evidence in patients who followed a strict supplementation protocol that, although they had mild to moderate vitamin deficiencies in the first 18 months (14.2% of patients included) after SADI-S, at 4 years, the cohort had zero nutritional deficiencies [49].

The spectrum of bariatric interventions is further widening with the exploration of non-surgical options. Endoscopic procedures like the placement of an adjustable gastric band or an intragastric balloon offer less invasive approaches for some patients. These devices can be inserted and adjusted through the mouth, promoting satiety and aiding in weight loss [50,51].

The future of bariatric surgery is likely to see a continued focus on minimally invasive techniques with the further refinement of existing procedures and the development of entirely new approaches. This, coupled with the exploration of non-surgical options, offers a more comprehensive toolbox for tackling the global obesity epidemic.

Fecal Microbiota Transfer (FMT): Another promising avenue for obesity treatment lies in manipulating the gut microbiota. Research suggests a strong link between the composition of gut bacteria and weight regulation [52,53]. FMT is a procedure where healthy, diverse gut bacteria from a donor are transplanted into the recipient’s gastrointestinal tract. The rationale behind FMT lies in the notion that a healthy gut microbiome can restore metabolic balance and promote weight loss in obese individuals. While still under investigation, FMT has shown promise in some studies. A recent meta-analysis and systematic review of FMT trials in obesity demonstrated significant improvements in body fat percentage, HbA1c, and insulin sensitivity [54,55]. However, there was no significant difference between the FMT groups and the placebo groups in terms of weight reduction. However, the long-term efficacy and safety of FMT require further exploration.

Pharmaceutical Advancements: Over the years, many anti-obesity medications (AOMs) have been tried to treat obesity, but most have been withdrawn because of safety concerns. For example, in early 2020, the US Food and Drug Administration (FDA) withdrew lorcaserin from the market because of evidence of increased cancer risk [56], and phentermine plus topiramate is approved only in the United States [57].

So, developing effective AOM has proven remarkably difficult due to both scientific and social complexities. Only in the past two decades have we gained a deep enough understanding of the molecular pathways regulating appetite to allow for a targeted approach to drug discovery. New agents that function by decreasing appetite or providing satiety have been approved by global food authorities over the past decade for chronic weight control [58], including bupropion plus naltrexone [59] and glucagon-like peptide-1 receptor agonists (GLP-1 RAs), with two familiar representatives: liraglutide and semaglutide [60].

The recent approval in 2021 by the FDA of semaglutide has marked a significant breakthrough in pharmaceutical interventions for obesity. These medications mimic the actions of a natural gut hormone, GLP-1, which promotes satiety, reduces appetite, and slows down stomach emptying [61,62].

Clinical trials have shown remarkable weight loss results with GLP-1 RAs, offering new hope for individuals struggling with obesity. Existing GLP-1 RAs, such as semaglutide, have demonstrated efficacy in achieving a weight loss of 15–17% [63,64,65]. However, even greater results are emerging with newer dual agonist GLP-1 RAs like tirzepatide, which has shown promise in clinical trials, with weight loss reaching up to 22.5% [66,67].

Researchers are actively exploring additional pharmaceutical targets that might influence factors like metabolism, fat storage, and energy expenditure.

Emerging Technologies: The fight against obesity extends beyond established methods. Novel brain stimulation therapies, along with the recent developments in the digital area offer promising tools for weight management, paving the way for more targeted and individualized approaches.

Brain Stimulation Therapies: Neuromodulation techniques like deep brain stimulation (DBS) are being explored for their potential roles in regulating appetite and food cravings. While still in the early stages of research, DBS offers a glimmer of hope for individuals with severe obesity who have not found success with traditional methods [68,69].

Cognitive Behavioral Therapy (CBT): Obesity is a complex condition with significant psychological and behavioral components. Cognitive behavioral therapy (CBT) has been shown to be effective in helping individuals develop healthy eating habits, increase physical activity levels, and manage stress—all crucial aspects of weight management. The integration of CBT alongside other treatment modalities offers a holistic approach to managing obesity and promoting long-term success [70,71].

Prescription Digital Therapeutics (PDTs): PDTs are revolutionizing weight management by offering FDA-approved apps and software programs that go beyond simple calorie counting. These personalized programs provide users with features like meal planning, behavior modification guidance, self-monitoring tools, and even virtual coaching—all conveniently accessible on a mobile device. PDTs create a comprehensive picture of health and empower individuals to take an active role in their weight loss journey [72,73,74].

Electroceuticals: Electroceuticals are emerging as a potentially groundbreaking, minimally invasive technology for weight management. These devices use strategically placed electrical stimulation to target nerves involved in appetite regulation. Early research suggests they might curb hunger pangs, modulate cravings, and improve satiety, offering a non-invasive and potentially targeted approach alongside established therapies [75,76].

Despite exciting advancements in future therapies, the current battle against obesity hinges on personalized strategies. Biomarkers like adipokines and genetic variations offer valuable insights, guiding tailored treatment plans. Techniques like minimally invasive surgical procedures and pharmaceutical advancements like GLP-1 RAs exemplify the promise of this personalized approach. However, achieving sustainable weight loss requires a multifaceted approach. By combining these advancements with established methods like diet and exercise, we can create a unique plan for each individual. This collaborative effort, leveraging both existing and emerging strategies, paves the way for a brighter future in obesity management. It empowers individuals to reclaim their health with a broader toolbox for combating this condition.

4.2. Diabetes Treatments

The discovery of insulin stands as a landmark achievement in the history of medicine, revolutionizing the treatment of diabetes. In the early 1900s, Nicolae Paulescu, a Romanian physiologist, conducted pioneering research on the pancreas. His work included isolating an extract with antidiabetic properties from the pancreas, which he called “pancreine” [77,78]. This crucial insight paved the way for subsequent advancements. Building upon this foundation, Frederick Banting’s successful isolation and clinical application of insulin in 1921 marked a pivotal moment in diabetes management [79].

This groundbreaking discovery continues to shape diabetes management today. While advancements in insulin delivery methods and formulations have occurred since the initial discovery, the core principle of insulin therapy remains a cornerstone of diabetes treatment. The legacy of insulin’s discovery extends far beyond its immediate impact, paving the way for ongoing research and the development of novel therapeutic approaches for diabetes.

Advancements in the insulin field: Traditional insulin formulations like regular and neutral protamine Hagedorn (NPH) insulin provided the initial foundation for diabetes management, offering control through varying onsets and durations of action. However, limitations like peak action mismatch for regular insulin and absorption variability for NPH insulin necessitated further advancements. The rise of newer insulin molecules addressed these concerns [80,81]. Rapid-acting analogs like lispro and glulisine mimic natural insulin release with a faster onset and shorter duration, ideal for postprandial control [82,83]. Short-acting analogs like aspart offer quicker action than regular insulin for pre-meal injections while minimizing hypoglycemia risk with their shorter duration [84,85]. Intermediate-acting analogs like glargine provide consistent, sustained release throughout the day, improving overall glycemic control [86,87]. Long-acting analogs like detemir or second-generation basal insulin, degludec, offer continuous basal insulin with extended durations, simplifying treatment regimens [88,89].

The relentless pursuit of improved glycemic control in diabetes management has driven the development of ever-longer-acting insulins. Following the success of intermediate-acting analogs like glargine, a new class of ultra-long-acting insulins has emerged. These insulins boast extended durations of action, potentially exceeding 40 h, and offer the promise of simplified treatment regimens with less frequent injections. The once-weekly insulin icodec exemplifies this advancement, offering a potential alternative to daily injections for both type 1 [90] and type 2 diabetes [91].

The phase three ONWARDS trials investigated the efficacy and safety of once-weekly icodec compared to daily degludec injections for both type 1 and type 2 diabetes [92]. The studies found that icodec was as effective, or even more effective, in reducing HbA1c levels compared to degludec. Additionally, icodec may improve treatment adherence due to the reduced injection frequency [93]. However, some limitations exist, including a slightly increased risk of hypoglycemia with icodec and a lack of long-term data on its safety and efficacy [90].

The future of insulin: While injectable insulin remains the mainstay of treatment for diabetes, it is not without its challenges. The risk of hypoglycemia and the need for strict adherence to daily injections can be significant disadvantages for many patients. Despite these issues, the quest for a convenient and non-invasive alternative continues. Oral insulin delivery has long been a coveted goal, and exciting research is exploring several promising avenues.

Sublingual Drops: Researchers at the University of British Columbia are developing fast-acting oral insulin drops that dissolve under the tongue. These drops bypass the digestive system and enter the bloodstream directly, potentially offering a quicker and more convenient alternative to injections for post-meal glucose control [94,95].

Nano-carrier encapsulated insulin: Another promising approach involves encapsulating insulin in microscopic carriers designed to protect it from stomach acid and deliver it effectively to the liver. This method holds promise for sustained insulin release, potentially mimicking the action of long-acting injectable insulin [96,97].

Glucose-responsive insulin tablets: These novel tablets exhibit a glucose-responsive release profile, delivering insulin only in response to elevated blood sugar levels. This approach achieves two key functionalities: overcoming intestinal epithelial barriers and acidic environments, as well as achieving the on-demand release of insulin only in response to rising blood sugar levels. A single dose of insulin delivered by this method significantly extended the therapeutic efficacy up to 16 h in a T1D mouse model [98].

These are just a few examples of ongoing research on oral insulin delivery. While challenges remain, such as ensuring sufficient absorption and controlled release, these advancements offer a glimpse into the future of diabetes management.

Beyond Insulin Therapy: new classes of medications are emerging, such as sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists, offering alternative mechanisms for blood sugar control.

SGLT2 inhibitors: These have emerged as a cornerstone therapy for T2D, demonstrating efficacy in glycemic control and offering a unique safety profile. However, recent advancements have unveiled a broader spectrum of benefits, extending their therapeutic impact beyond blood sugar management. SGLT2 inhibitors have shown effectiveness in lowering blood sugar levels and have even been demonstrated to offer additional benefits, such as reducing the risk of heart failure and kidney disease in individuals with type 2 diabetes [99,100,101,102]. While SGLT2 inhibitors offer a multitude of benefits, it is crucial to acknowledge their limitations. These agents are not a one-size-fits-all solution for T2D management. Potential side effects, such as urinary tract infections and diabetic ketoacidosis, require careful monitoring and patient education [99,103].

GLP-1 Receptor Agonists: Similar to their role in treating obesity, GLP-1 receptor agonists are emerging as promising treatments for type 2 diabetes. These medications stimulate the release of GLP-1, a gut hormone that promotes insulin secretion, reduces glucagon secretion (which raises blood sugar), and slows down stomach emptying. Clinical trials have shown promising results for improved blood sugar control and weight management in patients with type 2 diabetes [104,105,106].

Dual and triple incretin agonists: These medications combine the benefits of GLP-1 receptor agonists with another incretin hormone, GIP (glucose-dependent insulinotropic polypeptide), potentially offering enhanced glycemic control and additional benefits like improved gut health and a reduced risk of hypoglycemia [107,108,109].

Emerging technologies: The future of diabetes management gleams with promise, with continuous advancements in sensor technology and AI-powered algorithms paving the way for a future free from constant monitoring and toward proactive interventions.

Continuous Glucose Monitoring (CGM): This technology offers a significant leap forward in blood sugar monitoring. Instead of relying on finger pricks and sporadic blood sugar checks, CGM systems utilize a tiny sensor inserted under the skin to continuously monitor blood sugar levels in real-time. This continuous data stream provides a more comprehensive picture of glucose fluctuations throughout the day and night, allowing for better management of blood sugar levels and the identification of patterns that might otherwise go unnoticed [110,111]. Sensors are becoming more accurate and lasting longer, while minimally invasive options are being explored [112]. The future of CGM technology is looking even brighter with the development of implantable CGM systems. These small, biocompatible devices are inserted under the skin and can continuously monitor blood sugar levels for extended periods, typically ranging from 3 to 6 months [113,114,115]. CGM is also becoming more interconnected with other devices and cloud storage, allowing for better data sharing and remote monitoring by healthcare professionals [116,117].

Closed-loop insulin delivery systems: One of the most exciting advancements in diabetes management is the emergence of closed-loop insulin delivery systems, often referred to as “artificial pancreas” systems. These innovative devices integrate seamlessly with CGM technology. This closed-loop system mimics the natural function of a healthy pancreas, offering tighter blood sugar control, lowering the risk of hypoglycemia, and reducing the burden of constant monitoring and medication adjustments for patients [118,119]. While a fully autonomous artificial pancreas remains under development, the achievements in closed-loop systems to date and the swift pace of innovation highlight the immense potential for this technology to revolutionize diabetes treatment.

Stem cell therapy: Researchers are exploring various stem cell sources, including embryonic stem cells, induced pluripotent stem cells (iPSCs), and adult stem cells. iPSCs, derived from a patient’s own skin cells and reprogrammed to an embryonic-like state, hold particular promise, as they can potentially reduce the risk of immune rejection [120,121]. Despite the immense potential, there are significant challenges to overcome. Ethical considerations surrounding embryonic stem cells and the potential for tumor formation with certain types of stem cells require careful evaluation. Additionally, ensuring the long-term survival and function of transplanted stem cells within the body remains a hurdle [120,122,123]. With continued research and development, stem cell therapy has the potential to revolutionize diabetes treatment and ultimately lead to a cure.

Glycemic Variability (GV): Beyond absolute blood sugar levels, researchers are increasingly focusing on glycemic variability (GV), which refers to wide swings in blood sugar levels throughout the day. High GV is associated with an increased risk of diabetes complications, even if average blood sugar levels fall within the normal range. New technologies like CGM are facilitating the measurement of GV, allowing healthcare professionals to tailor treatment plans that not only focus on lowering blood sugar but also aim to minimize these harmful fluctuations [124,125,126].

Hydrogels: These three-dimensional networks of water and polymers are emerging as versatile materials for various diabetes management applications. Their biocompatibility and customizability allow for integration with glucose-sensitive enzymes in CGM sensors, the development of hydrogels responsive to blood sugar fluctuations for smart insulin delivery, the creation of moist wound-healing environments for diabetic foot ulcers, and the encapsulation of insulin-producing cells for cell transplantation therapies [127,128,129,130]. The tailorable properties of hydrogels, including self-healing abilities, along with continuous advancements in incorporating biosensors, drug delivery mechanisms, and closed-loop systems, position them at the forefront of innovative diabetes treatment strategies.

Artificial intelligence (AI) and machine learning (ML): These technologies are revolutionizing diabetes management. AI algorithms can analyze CGM data to predict glucose levels and personalize insulin delivery in closed-loop systems. Additionally, ML holds promise for risk stratification, allowing for early intervention [39,131,132,133,134]. AI-powered virtual assistants and chatbots can further empower patients through education and medication reminders. As AI and ML technology advances, integration with wearables, genetic data, and decision support systems holds immense potential for personalized and effective diabetes management strategies.

Ultrasound Neuromodulation with liver-targeted peripheral focused ultrasound stimulation (pFUS): pFUS shows to be a promising new treatment modality that could be used as a non-pharmaceutical adjunct or even an alternative to current drug treatments in diabetes. The technique has already demonstrated its effectiveness in alleviating obesity and obesity-related complications in an in vitro study on mice [131,134]. More recently, it was demonstrated in a phase one clinical trial to reduce homeostatic model assessment for insulin resistance (HOMA-IR) scores by lowering fasting insulin [135,136]. This non-invasive procedure uses ultrasound waves to modulate nerve activity and liver functions, thereby influencing glucose and lipid metabolism, with promising applications in obesity treatment, based on the utilization of a specially designed ultrasound system that is equipped with software allowing for controlled pulsed ultrasound stimulation [137]. The attending physician, upon identifying the area of interest through ultrasound imaging, activates the pulsed stimulus using a control button. Both the imaging and treatment procedures are conducted using a single curved abdominal transducer [136]. By stimulating specific regions of the liver, particularly the hepatic nerves, pFUS can potentially reduce inflammation and insulin resistance and improve metabolic control, which are critical factors in managing obesity and diabetes [135,136,137].

These advancements paint a hopeful picture for the future of diabetes management. The integration of these novel treatments with traditional therapies offers the potential for more personalized and effective management strategies, ultimately improving the quality of life for individuals living with diabetes. Furthermore, the ongoing research on cellular therapies holds promise for a future free from the burden of diabetes.

5. Managing Obesity and Type 2 Diabetes

Obesity and T2D are intricately linked conditions that often coexist, creating a significant clinical challenge. Excess weight, particularly around the waist, impairs the body’s ability to utilize insulin effectively, leading to insulin resistance—a hallmark of T2D. Conversely, chronically elevated blood sugar levels in T2D further contribute to weight gain by creating an environment where the body prioritizes fat storage over burning it for energy. This vicious cycle underscores the importance of a comprehensive approach to managing both conditions simultaneously.

Fortunately, the advancements discussed in this review hold immense promise for their comprehensive care. Here is how these novel approaches can be specifically applied to comorbidity management:

Hydrogels: These versatile materials can play a crucial role. Implantable hydrogels loaded with medications like insulin could offer targeted and sustained release, improving glycemic control while promoting weight loss through glucagon-like peptide-1 (GLP-1) analogs [127,128,129,130]. Additionally, self-healing hydrogels could enhance patient comfort and reduce the need for frequent replacements.

Ultrasound Neuromodulation (pFUS): This non-invasive technique shows promise for tackling the underlying causes of both conditions. By targeting the liver with focused ultrasound waves, pFUS may reduce inflammation and improve insulin sensitivity, leading to better blood sugar control and potentially aiding in weight management [135,136,137]. Further research is needed to explore the long-term efficacy and optimal treatment protocols for patients with this comorbidity.

AI and Machine Learning (ML): These technologies can personalize treatment plans by analyzing a patient’s CGM data, weight trends, and other factors. AI-powered systems can predict blood sugar fluctuations and adjust insulin delivery accordingly in closed-loop systems. ML algorithms can also identify high-risk individuals for early intervention, allowing for preventative measures to manage both obesity and T2D.

By combining these advancements with traditional therapies like dietary modifications and exercise programs, healthcare professionals can create a more comprehensive and effective treatment approach for patients with obesity and T2D. This integrated approach has the potential to significantly improve their quality of life and overall health outcomes.

6. Limitations

Despite providing a comprehensive overview of advancements in the diagnosis and treatment of obesity and diabetes, this review has several limitations. First, due to the rapid pace of research and development in these fields, some of the most recent innovations may not have been included. Additionally, while the review highlights promising new treatments and technologies, it does not delve deeply into the potential long-term efficacy and safety concerns associated with these novel approaches. Moreover, the review lacks a detailed discussion on the socioeconomic and accessibility issues that might impact the widespread adoption of these advanced treatments. The integration of emerging technologies and personalized medicine approaches into existing healthcare systems poses significant logistical and ethical challenges, which are not fully addressed. Additionally, exploring how these advancements can be tailored to meet the specific needs of diverse patient populations, such as children and pregnant women, would be valuable for a more holistic understanding. Furthermore, the focus of the review is predominantly on advancements in high-income countries, potentially overlooking the unique challenges faced by low- and middle-income regions in managing obesity and diabetes. These limitations underscore the need for continuous research and a more inclusive approach to effectively address the global burden of these diseases.

7. Conclusions

This review paints a hopeful picture for the future of managing obesity and diabetes. We are witnessing a significant departure from the limitations of traditional methods, with a clear shift toward personalized and precise medicine. In obesity treatment, a multifaceted approach is emerging, encompassing minimally invasive bariatric procedures, microbiota manipulation through fecal transplants, innovative medications like GLP-1 receptor agonists, and exciting technological advancements like brain stimulation therapies and digital therapeutics—all aimed at achieving sustainable weight loss.

Diabetes management is undergoing a similar revolution. The continuous evolution of insulin formulations, the introduction of SGLT2 inhibitors and GLP-1 receptor agonists, and groundbreaking technologies like continuous glucose monitoring and closed-loop insulin delivery systems are transforming how we manage this condition. These advancements have accelerated significantly in recent years, providing continuous and precise glucose monitoring and insulin administration.

Furthermore, groundbreaking research avenues in stem cell therapy, AI-powered solutions, and glycemic variability monitoring hold immense promise for even more personalized and effective treatment strategies in the future. These collective advancements underscore the crucial role of an integrated, patient-centric approach in combating obesity and diabetes. This comprehensive strategy offers renewed hope for improved health outcomes and provides a better quality of life for individuals living with these conditions.