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.

Novel Application of Microdosing Glucagon for Hypoglycemia After Total Pancreatectomy and Autologous Islet Transplant.

Total pancreatectomy and autologous islet transplantation (TPAIT) is a procedure to ameliorate dysglycemia associated with post-pancreatectomy. Patients who undergo TPAIT are at risk of developing hypoglycemia postoperatively. The current literature suggests that hypoglycemia may be due to a glucagon-deficiency state. To date, there is minimal literature available that explores treatment options to minimize hypoglycemia in these patients. In this case, a 29-year-old female patient was administered a microdosing glucagon protocol post TPAIT and experienced improvements in hypoglycemia. We describe the dosing regimen of the protocol and provide continuous glucose monitoring data to support our findings. This case adds to the limited evidence on effective treatment options for these rare patients. To our knowledge, this is the first application of a microdosing glucagon protocol to treat hypoglycemia associated with TPAIT.

Reduction in Opiate Use, Pain, Nausea, and Length of Stay After Implementation of a Bariatric Enhanced Recovery After Surgery Protocol.

PURPOSE: Evaluate adherence to bariatric surgery enhanced recovery after surgery (ERAS) protocols in pre-operative, operative, and post-operative phases, and to compare opiate use, nausea control, and length of stay (LOS) versus historical controls. MATERIALS AND METHODS: A retrospective, observational cohort study was conducted to evaluate adherence to ERAS protocols and compare opiate and antiemetic use, pain intensity, and LOS versus those of traditional care (TC) patients preceding protocol implementation at Erie County Medical Center, a community-based hospital in Buffalo, NY, USA. RESULTS: One hundred ERAS and TC patients were compared. Patients were similar in age (42.5 years), gender (female, ~ 80%), race (~ 80 white), and BMI (47 kg/m2). The primary procedure performed was sleeve gastrectomy (89% ERAS, 86% TC). Protocol adherence was high for ERAS phases: prior to admission (85-98%), pre-operative (96-100%), operative (93-99%), post-anesthesia care unit (PACU) (55-61%), and floor (86-98%). Opiate morphine milligram equivalent (MME) was reduced in ERAS vs. TC in hospital by 73% (43.5 ± 42.4 vs. 160 ± 116; p < 0.001), discharge prescribing by 53% (34.8 ± 38.2 vs. 74 ± 125 MME; p = 0.003), and in total by 69% (78.3 ± 67.5 vs. 252 ± 160; p < 0.001). Despite lower opiate use, ERAS had lower pain intensity entering PACU (1.1 ± 1.8 vs. 1.9 ± 2.6; p < 0.011), leaving PACU (1.7 ± 1.5 vs. 2.9 ± 1.5; p < 0.001), and floor day 0 (5.0 ± 2.1 vs. 5.9 ± 1.8; p < 0.001). Fewer ERAS required antiemetic day 0 (63% vs. 94%; p < 0.001). ERAS were discharged in fewer hours than TC (41.1 ± 15.5 vs. 52.1 ± 18.9 h; p < 0.001). CONCLUSIONS: Bariatric surgery ERAS protocols were implemented with a high rate of adherence and yielded profound reduction in operative and post-operative opiate use while improving pain control and nausea management in hospital and decreasing LOS.