A Review of Incretin Therapies Approved and in Late-Stage Development for Overweight and Obesity Management.

OBJECTIVE: To review clinical trial data for incretin therapies that are approved or in late-stage development for overweight or obesity management, along with clinical implications of these therapies and future directions. METHODS: We searched for clinical trials involving incretin therapies studied specifically for overweight or obesity management in ClinicalTrials.gov and PubMed from registry inception through December 2023. RESULTS: Glucagon-like peptide-1 (GLP-1) receptor agonism, alone and in combination with glucose-dependent insulinotropic polypeptide (GIP) receptor agonism or glucagon agonism, leads to significant weight reduction in people with overweight or obesity. Newer incretin therapies have demonstrated weight reduction between 15% to 25%, far outpacing non-incretin therapies for weight management and achieving levels of weight loss that may prevent weight-related complications. However, the discontinuation of incretin therapies is associated with weight regain. The main side effects of incretin therapies are transient, mild-to-moderate gastrointestinal side effects - nausea, diarrhea, constipation, and vomiting - that commonly occur in the first 4 to 8 weeks of treatment. There is a rich late-stage pipeline of incretin therapies for weight management, consisting of oral GLP-1 receptor agonists, dual GLP-1/GIP receptor agonists, dual GLP-1/glucagon receptor agonists, triple GLP-1/GIP/glucagon receptor agonists, and combination therapies with nonincretin drugs. CONCLUSION: Newer incretin therapies for weight management have the potential to improve the treatment for overweight and obesity, the treatment and prevention of weight-related complications, and the individualization of weight management. Ensuring that these therapies are accessible - and that treatment with them is consistent and sustainable - is necessary to translate findings from trials into the real world.

Continuous Glucose Monitoring Using the Dexcom G6 in Cardiac Surgery During the Postoperative Period.

OBJECTIVE: Cardiac surgery is associated with hyperglycemia, which in turn is associated with adverse postsurgical outcomes such as wound infections, acute renal failure, and mortality. This pilot study seeks to determine if Dexcom G6Pro continuous glucose monitor (Dexcom G6Pro CGM) is accurate during the postoperative cardiac surgery period when fluid shifts, systemic inflammatory response syndrome, and vasoactive medications are frequently encountered, compared to standard glucose monitoring techniques. METHODS: This study received institutional review board approval. In this prospective study, correlation between clinical and Dexcom glucose readings was evaluated. Clinical glucose (blood gas, metabolic panel, and point of care) data set included 1428 readings from 29 patients, while the Dexcom G6Pro CGM data included 45 645 data points following placement to upper arm. Additionally, average clinical measurements of day and overnight temperatures and hemodynamics were evaluated. Clinical and Dexcom data were restricted to being at least 1 hour after prior clinical reading Matching Dexcom G6Pro CGM data were required within 5 minutes of clinical measure. Data included only if taken at least 2 hours after Dexcom G6Pro CGM insertion (warm-up time) and analyzed only following intensive care unit (ICU) admission. Finally, a data set excluding the first 24 hours after ICU admission was created to explore stability of the device. Patients remained on Dexcom G6Pro CGM until discharge or 10 days postoperatively. RESULTS: The population was 71% male, 14% with known diabetes; 66% required intravenous insulin infusion. The Clarke error grid plot of all measures post-ICU admission showed 53.5% in zone A, 45.9% in zone B, and 0.6% (n = 5) in zones D or E. The restricted dataset that excluded the first 24 hours post-ICU admission showed 55.9% in zone A, 43.9% in zone B, and 0.2% in zone D. Mean absolute relative difference between clinical and Dexcom G6Pro CGM measures was 20.6% and 21.6% in the entire post-ICU admission data set, and the data set excluding the first 24 hours after ICU admission, respectively. In the subanalysis of the 12 patients who did not have more than a 5-minute tap in the operating room, a consensus error grid, demonstrated that after ICU admission, percentage in zone A was 53.9%, zone B 45.4%, and zone C 0.7%. Similar percentages were obtained removing the first 24 hours post-ICU admission. These numbers are very similar to the entire cohort. A consensus error grid created post-ICU admission demonstrated: (zone A) 54%, (zone B) 45%, (zone C) 0.9%, and the following for the dataset created excluding the first 24 hours: (zone A) 56%, (zone B) 44%, (zone C) 0.4%, which demonstrated very close agreement with the original Clarke error grid. No adverse events were reported. CONCLUSIONS: Almost 100% of Dexcom G6Pro CGM and clinical data matching points fell within areas considered as giving clinically correct decisions (zone A) and clinically uncritical decisions (zone B). However, the relatively high mean absolute relative difference precludes its use for both monitoring and treatment in the clinical context. As technology evolves, interstitial glucose monitoring may become an important tool to limit iatrogenic anemia and mitigate glycemic fluctuations.

Patient Perceptions of Satisfaction and Quality of Life Regarding Use of a Novel Insulin Delivery Device.

Advances in insulin delivery technologies have led to the development of tubeless "patch" systems; however, these devices still involve a level of complexity. We surveyed individuals with type 1 or type 2 diabetes to explore their attitudes and satisfaction after using the CeQur Simplicity insulin patch (SIP) for 2 months. Transition to the SIP yielded significant increases in respondents' overall treatment satisfaction, less diabetes burden, and improvements in psychological well-being compared with respondents' prior insulin delivery method.

Expert Roundtable on Continuous Glucose Monitoring.

OBJECTIVE: The objective of this study was to define an expert opinion on continuous glucose monitoring (CGM) in persons with type 2 diabetes mellitus, including its advantages, barriers, and best clinical practices for initiation, patient-clinician communication, and data management. METHODS: A series of virtual discussions was held to recommend improvements to clinical practice and design clinical tools for primary care clinicians. Participants included endocrinologists, primary care physicians, physician assistants, advanced practice nurses, and diabetes care and education specialists. RESULTS: The expert panels recommended CGM as a supplement to blood glucose monitoring and hemoglobin A1c for managing diabetes in persons with diabetes (PWDs). CGM can help predict potential pitfalls in glycemic management, including hypo and hyperglycemic excursions, which directly influence lifestyle changes, medication initiation, and dosing decisions. A toolkit was designed with practical guidance on the integration of CGM into clinical practice, interpretation of results, clinical guidelines, a patient action plan, and other useful management tools. CONCLUSION: This review summarizes the findings from a roundtable discussion with endocrinology and primary care clinicians, a discussion of the advantages and challenges of CGM, and clinical approaches to improving the care of PWDs. CGM offers more detailed tracking of glucose levels than blood glucose monitoring or hemoglobin A1c, and it can detect asymptomatic hypoglycemia. Specialized education of providers, the cost to patients and providers, and data management are barriers to the widespread adoption of CGM for PWDs.

Closed-Loop Artificial Pancreas Therapy for Type 1 Diabetes.

PURPOSE OF REVIEW: Closed-loop insulin pump systems (artificial pancreas) represent the cutting edge of insulin delivery technology. There are only a few systems currently approved for use in the USA: the MiniMed 670G/770G (which share an algorithm), t:slim X2 Control IQ, and the Omnipod 5. We review these systems and look into the future of the technology. RECENT FINDINGS: All of the approved closed-loop insulin pump systems have demonstrated in multicenter prospective trials improvements in time in range, hemoglobin A1c, and time spent in hypoglycemia. The newer systems have also improved time spent in automation. Comparisons between the systems with regard to glycemic control are difficult to make due to differences in clinical trial design, but there are notable differences in the user experience between systems. The past few years have been a time of exponential development in the field of closed-loop insulin pump systems. However, more research is needed to provide full automation of these systems without any need for information from the user.

Optimizing Therapeutic Outcomes With Oral Semaglutide: A Patient-Centered Approach.

In September 2019, the U.S. Food and Drug Administration approved oral semaglutide as the first orally administered glucagon-like peptide 1 (GLP-1) receptor agonist for treating people with type 2 diabetes. Although injectable GLP-1 receptor agonists are well-established treatment options for people with type 2 diabetes, clinical experience with an oral formulation in this class is limited. This article provides practical guidance for diabetes care and education specialists on how to effectively counsel patients initiating therapy with oral semaglutide on appropriate administration of the treatment and its possible effects on glycemic control, body weight, and quality of life. Strategies for mitigating potential side effects typical of the GLP-1 receptor agonist class, namely nausea, vomiting, and diarrhea, are also provided. Involving patients in treatment decisions and educating them about available and prescribed medications are key strategies for encouraging treatment adherence and ensuring optimal therapeutic outcomes.

Why Are We Stuck? Therapeutic Inertia in Diabetes Education.

Diabetes educators can be challenged by therapeutic inertia, as has been documented with other health care providers. There are many contributing factors related to the educators themselves, their patients, and the health care system in which they operate. To address this potentially significant barrier to quality patient care, diabetes educators can adopt numerous strategies to maximize their impact and address the factors contributing to therapeutic inertia in their practices.

Adjunct Antihyperglycemic Agents in Overweight and Obese Adults With Type 1 Diabetes.

OBJECTIVE: People with type 1 diabetes often have suboptimal glycemic control. The gold standard of treatment is basal-bolus insulin or subcutaneous insulin infusion via insulin pump. Although insulin therapy improves glycemic control, weight gain and hypoglycemia often limit achievement of hemoglobin A1C (A1C) goals. The number of people with type 1 diabetes who are overweight or obese is increasing, and there are many similarities between what was historically called type 1 and type 2 diabetes. Therefore, there is rationale for using antihyperglycemic agents that target other pathophysiological abnormalities to facilitate weight loss and improve glycemic control. DATA SOURCES: We performed a MEDLINE search from 1975 through October 2018 to identify articles that studied noninsulin agents in adults with type 1 diabetes and body mass index (BMI) ≥25 kg/m2. STUDY SELECTION AND DATA EXTRACTION: Identified articles were included if the study duration was ≥4 weeks, included ≥20 patients, and set mean baseline BMI ⩾25kg/m2. DATA SYNTHESIS: This review summarizes 32 clinical trials. Amylin mimetics, sodium-glucose-like transporter-2 inhibitors, and glucagon-like-peptide-1 receptor agonists demonstrate the greatest improvements in body weight and A1C. The most common adverse effects are hypoglycemia and ketosis. Relevance to Patient Care and Clinical Practice: Patients with type 1 diabetes may have interest in starting noninsulin agents. Clinicians need to be knowledgeable in the efficacy and adverse effect profile of these agents, specifically in people with type 1 diabetes. CONCLUSIONS: Adding noninsulin antihyperglycemic agents may benefit select overweight or obese adults with type 1 diabetes. These agents are off-label, and if used, close monitoring is essential.

Diabetes technology: A primer for clinicians.

Diabetes technology is evolving rapidly and is changing the way both patients and clinicians approach the management of diabetes. With more devices gaining US Food and Drug Administration approval and insurance coverage expanding, these new technologies are being widely adopted by people living with diabetes. We provide a summary of the commonly available devices in the market today that clinicians will likely encounter. This includes continuous glucose monitors (CGMs); connected insulin pens, caps, and buttons; and insulin pumps. Clinicians' awareness of and familiarity with this technology will enhance its accessibility for patients with diabetes.

Removing Barriers, Bridging the Gap, and the Changing Role of the Health Care Professional with Automated Insulin Delivery Systems.

As all people with type 1 diabetes (T1D) and some with type 2 diabetes (T2D) require insulin, there is a need to develop management methods that not only achieve glycemic targets but also reduce the burden of living with diabetes. After insulin pumps and continuous glucose monitors, the next step in the evolution of diabetes technology is automated insulin delivery (AID) systems, which have transformed intensive insulin management over the past decade, as these systems address the shortcomings of previous management options. However, AID use remains fairly limited, and access represents a major barrier to use for many people with diabetes, despite these systems being standard of care. Therefore, the future of AID will necessitate addressing barriers related to social determinants of health, finances, and an expansion of the number and type of health care professionals (HCPs) prescribing AID systems. These crucial steps will be essential to ensure that everyone with intensively managed diabetes can use AID systems. The impact of implementing these changes will create a shift in the future of diabetes care that will result in achievement of more targeted glycemia and psychosocial outcomes for all people with diabetes and an expansion of the role of all HCPs in AID-related diabetes care. Even more importantly, by addressing social determinants of health and clinical inertia related to AID, the field can address disparities in outcomes across countries, race, gender, socioeconomic status, and insurance status. Furthermore, the increased use of AID system will provide more time during appointments for a shift in the discussion away from fine tuning insulin dosing and toward a focus on more topics related to behavior and conversations about general health. This will include psychosocial outcomes, and quality of life. In addition, these changes can hopefully allow for time to discuss more general issues, such as cardiovascular health, obesity prevention, diabetes-related complications, and other health-related concerns.

Opportunities to overcome underutilization of enhanced insulin delivery technologies in people with type 2 diabetes: a narrative review.

Use of innovative technologies such as continuous glucose monitoring (CGM) and insulin delivery systems have been shown to be safe and effective in helping patients with diabetes achieve significantly improved glycemic outcomes compared to their previous therapies. However, these technologies are underutilized in many primary care practices. This narrative review discusses some of the clinical and economic benefits of tubeless insulin delivery devices and discusses how this technology can overcome the main obstacles inherent to use of conventional insulin delivery devices.

Behavioral Engagement and Activation Model Study (BEAMS): A latent class analysis of adopters and non-adopters of digital health technologies among people with Type 2 diabetes.

Many people with Type 2 diabetes (T2D) who could benefit from digital health technologies (DHTs) are either not using DHTs or do use them, but not for long enough to reach their behavioral or metabolic goals. We aimed to identify subgroups within DHT adopters and non-adopters and describe their unique profiles to better understand the type of tailored support needed to promote effective and sustained DHT use across a diverse T2D population. We conducted latent class analysis of a sample of adults with T2D who responded to an internet survey between December 2021 and March 2022. We describe the clinical and psychological characteristics of DHT adopters and non-adopters, and their attitudes toward DHTs. A total of 633 individuals were characterized as either DHT "Adopters" (n = 376 reporting any use of DHT) or "Non-Adopters" (n = 257 reporting never using any DHT). Within Adopters, three subgroups were identified: 21% (79/376) were "Self-managing Adopters," who reported high health activation and self-efficacy for diabetes management, 42% (158/376) were "Activated Adopters with dropout risk," and 37% (139/376) were "Non-Activated Adopters with dropout risk." The latter two subgroups reported barriers to using DHTs and lower rates of intended future use. Within Non-Adopters, two subgroups were identified: 31% (79/257) were "Activated Non-Adopters," and 69% (178/257) were "Non-Adopters with barriers," and were similarly distinguished by health activation and barriers to using DHTs. Beyond demographic characteristics, psychological, and clinical factors may help identify different subgroups of Adopters and Non-Adopters.

In this study, we characterized subgroups of adopters and non-adopters of digital health technologies (DHTs) for managing Type 2 diabetes, such as apps to track nutrition, continuous glucose monitors, and activity monitors like Fitbit. Self-efficacy for diabetes management, health activation, and perceived barriers to use DHT emerged as characteristics that distinguished subgroups. Notably, subgroups of adopters differed in their interest to use these technologies in the next 3 months; groups with low levels of self-efficacy and health activation were least interested in using them and thus at risk of discontinuing use. The ability to identify these subgroups can inform strategies tailored to each subgroup that motivate adoption of DHTs and promote long-term engagement.

Expert Panel Recommendations for a Standardized Ambulatory Glucose Profile Report for Connected Insulin Pens.

Background: Connected insulin pens capture data on insulin dosing/timing and can integrate with continuous glucose monitoring (CGM) devices with essential insulin and glucose metrics combined into a single platform. Standardization of connected insulin pen reports is desirable to enhance clinical utility with a single report. Methods: An international expert panel was convened to develop a standardized connected insulin pen report incorporating insulin and glucose metrics into a single report containing clinically useful information. An extensive literature review and identification of examples of current connected insulin pen reports were performed serving as the basis for creation of a draft of a standardized connected insulin pen report. The expert panel participated in three virtual standardization meetings and online surveys. Results: The Ambulatory Glucose Profile (AGP) Report: Connected Insulin Pen brings all clinically relevant CGM-derived glucose and connected insulin pen metrics into a single simplified two-page report. The first page contains the time in ranges bar, summary of key insulin and glucose metrics, the AGP curve, and detailed basal (long-acting) insulin assessment. The second page contains the bolus (mealtime and correction) insulin assessment periods with information on meal timing, insulin-to-carbohydrate ratio, average bolus insulin dose, and number of days with bolus doses recorded. The report's second page contains daily glucose profiles with an overlay of the timing and amount of basal and bolus insulin administered. Conclusion: The AGP Report: Connected Insulin Pen is a standardized clinically useful report that should be considered by companies developing connected pen technology as part of their system reporting/output.

Advantages and disadvantages of connected insulin pens in diabetes management.

Insulin administration remains vital to the treatment of diabetes and although there have been advances in insulin delivery, evidence suggests that many people with diabetes on insulin therapy have suboptimal glycemic management. Recent advancements in insulin administration techniques include connected insulin devices, such as connected insulin pens and pen caps. In this review, we provide an overview of the literature on the use of connected insulin pens and pen caps to further elucidate the clinical benefits and drawbacks of these devices. We discuss the development of these devices, outlining the characteristics of insulin pens and pen caps with regulatory approvals. These devices have different features that can ease the burden of diabetes management, including automatic recording of insulin dose information, tracking of insulin-on-board, bolus calculators, and missed dose alerts. Despite the advantages of connected pens and pen caps, a small percentage of insulin users are currently using these devices, due to many factors, including lack of health-care professional awareness, initial training for prescribers, and setup of the device. Overcoming these barriers and publishing more data demonstrating the glycemic outcomes associated with these systems could improve diabetes management for people living with diabetes. As health-care systems become increasingly digital, connected insulin pens have the potential to allow a data-driven approach to diabetes management for people who are not interested in, cannot afford, or do not have intensive insulin regimens that might warrant use of insulin pumps or automated insulin delivery systems.

Prevalence of Sodium Glucose Cotransporter 2 (SGLT-2) Inhibitor Prescribing in Patients with Type 2 Diabetes Mellitus and Reduced Estimated Glomerular Filtration Rate.

Sodium glucose cotransporter 2 (SGLT-2) inhibitors have demonstrated benefit in people with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD), including slowing the progression of CKD and lowering the risk of kidney failure and death. Despite this evidence, literature suggests SGLT-2 inhibitors are underutilized in this population. To assess prescribing practices and identify potential variables predictive of SGLT-2 inhibitor prescribing, a non-interventional, retrospective, cross-sectional study was conducted in patients with T2DM and reduced estimated glomerular filtration rate (eGFR). The primary outcome compared prevalence of SGLT-2 inhibitor prescribing in patients with T2DM and eGFR of 30-44 mL/min/1.73m2 to patients with T2DM and eGFR 45-59 mL/min/1.73m2. The secondary outcome described possible predictors of prescribing SGLT-2 inhibitors in this population. Of the 9,387 patients identified with T2DM and reduced eGFR, an SGLT-2 inhibitor was prescribed to 324 (12.2%) patients with eGFR of 30-44 mL/min/1.73m2 versus 799 (11.9%) patients with eGFR of 45-59 mL/min/1.73m2. Patients more likely to be prescribed SGLT-2 inhibitors were younger, male, had a higher body mass index (BMI), a higher hemoglobin A1c (HbA1c), were on other antihyperglycemic medications, had concomitant cardiovascular disease, or had concomitant heart failure. This study found no significant difference in prevalence of SGLT-2 inhibitor prescribing between patients with T2DM and eGFR 30-44 mL/min/1.73m2 versus eGFR 45-59 mL/min/1.73m2 (p=0.70). Further exploration into the causes of low SGLT-2 inhibitor prescribing prevalence is warranted given the growing evidence supporting the use of these agents in patients with T2DM and reduced renal function.

Significant publications in diabetes pharmacotherapy and technology in 2020.

INTRODUCTION: The most significant articles on diabetes pharmacotherapy and technology in the peer-reviewed literature from 2020, as determined by a panel of pharmacists with expertise in diabetes care and education, are summarized. AREAS COVERED: Members of the Association of Diabetes Care and Education Specialists Pharmacy Community of Interest were selected to review articles published in prominent peer-reviewed journals in 2020 that most impacted diabetes pharmacotherapy and technology. A list of 37 nominated articles were compiled (22 in diabetes pharmacotherapy and 15 in diabetes technology). Based on discussion among the authors, the articles were ranked based on significant contribution, impact, and diversity to diabetes pharmacotherapy and technology. The top 10 highest ranked publications (n = 6 for diabetes pharmacotherapy and n = 4 in diabetes technology) are summarized in this article. EXPERT OPINION: With the significant number of publications in diabetes care and education, it can be challenging and overwhelming to remain current with published literature. This review article may be helpful in identifying key articles in diabetes pharmacotherapy and technology from the year 2020.

Association of SGLT-2 Inhibitors With Treatment Satisfaction and Diabetes-Specific and General Health Status in Adults With Cardiovascular Disease and Type 2 Diabetes.

Background It is unknown if initiation of a sodium-glucose cotransporter-2 inhibitor (SGLT-2i) is associated with changes in patient-reported health status outside of clinical trials. Methods and Results Using a prospective observational study design, adults with type 2 diabetes and cardiovascular disease were recruited from 14 US hospitals between November 2019 and December 2021 if they were new users of noninsulin antidiabetic medications. The primary outcome was change in 6-month diabetes treatment satisfaction. Secondary outcomes included diabetes-related symptom distress, diabetes-specific quality of life, and general health status for all patients and based on cardiovascular disease type. Inverse probability of treatment weight using propensity score was performed to compare outcome changes based on medication use. Of 887 patients (SGLT-2i: n=242) included in the inverse probability of treatment weight analyses, there was no difference in changes in treatment satisfaction in SGLT-2i users compared with other diabetes medication users (0.99 [95% CI, -0.14 to 2.13] versus 1.54 [1.08 to 2.00], P=0.38). Initiating an SGLT-2i versus other diabetes medications was associated with a greater reduction in ophthalmological symptoms (-3.09 [95% CI, -4.99 to -1.18] versus -0.38 [-1.54 to 0.77], P=0.018) but less improvement in hyperglycemia (1.08 [-2.63 to 4.79] versus -3.60 [-5.34 to -1.86], P=0.026). In subgroup analyses by cardiovascular disease type, SGLT-2i use was associated with a greater reduction in total diabetes symptom burden and neurological sensory symptoms in patients with heart failure. Conclusions Among patients with type 2 diabetes and cardiovascular disease, initiating an SGLT-2i was not associated with changes in diabetes treatment satisfaction, total diabetes symptoms, diabetes-specific quality of life, or general health status.

11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes-2023.

The American Diabetes Association (ADA) "Standards of Care in Diabetes" includes the ADA's current clinical practice recommendations and is intended to provide the components of diabetes care, general treatment goals and guidelines, and tools to evaluate quality of care. Members of the ADA Professional Practice Committee, a multidisciplinary expert committee, are responsible for updating the Standards of Care annually, or more frequently as warranted. For a detailed description of ADA standards, statements, and reports, as well as the evidence-grading system for ADA's clinical practice recommendations and a full list of Professional Practice Committee members, please refer to Introduction and Methodology. Readers who wish to comment on the Standards of Care are invited to do so at professional.diabetes.org/SOC.