Daily Endocrinology Research Analysis

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1 RA) reduce cardiovascular and kidney risk in patients with type 2 diabetes (T2D), yet real-world use remains suboptimal. Remote care models offer a promising approach to improve access; there is limited data on the safety of and adverse events (AEs) associated with prescribing and titrating these therapies through a protocol-driven remote management program. METHODS: The DRIVE trial was a pragmatic, randomized clinical trial evaluating the safety of a remote disease management program that initiated SGLT2i and/or GLP1 RA in patients with T2D and elevated cardiovascular or kidney risk. Participants were enrolled at a large integrated health care system in Massachusetts between March 2021 and December 2022. Participants were randomized to one of two implementation strategies: a sequential approach (two months of education first followed by medication initiation) or a bundled approach (simultaneous education and medication initiation). Non-clinical navigators and clinical pharmacists, supervised by physicians, oversaw medication initiation and monitoring under a collaborative drug therapy management agreement and protocol that included algorithms for initiation and titration of SGLT2i and GLP1 RA, as well as adjustment of concurrent glucose-lowering medications to reduce the risk of hypoglycemia Safety outcomes were collected through chart review and patient report, including targeted AEs, hospitalizations, emergency department visits, and urgent care visits. Targeted AEs were prospectively collected over the first six months after enrollment: for SGLT2i initiators, symptoms of genital mycotic infection, urinary tract infection, or volume depletion; for GLP 1 RA initiators, nausea, vomiting, diarrhea, and abdominal pain. Hospitalizations, emergency department visits, and urgent care visits over the first six months after enrollment were retrospectively collected through electronic health record review. RESULTS: Of 200 participants enrolled, 106 (53%) initiated SGLT2i (n=68) or GLP1 RA (n=40). Among SGLT2i users, 29.4% reported an AE, most commonly genital mycotic infections (10.3%) and symptoms of volume depletion (11.8%); 10.3% discontinued due to AEs. Among GLP1 RA users, 55.0% experienced AEs, predominantly gastrointestinal; 10.0% discontinued due to AEs. No severe hypoglycemia, emergency department visits, or hospitalizations occurred. CONCLUSIONS: A remote, pharmacist- and navigator-led program safely initiated SGLT2i and GLP1 RA in a high-risk T2D population, with AE rates comparable to clinical trials and high persistence. These findings support the feasibility of remote prescribing with appropriate clinical oversight and structured AE management. TRIAL REGISTRATION: Registry: ClinicalTrials.gov; URL: https://clinicaltrials.gov/study/NCT06046560; unique identifier: NCT06046560.

Impaired muscle strength and mitochondrial functionality are hallmarks of type 2 diabetes (T2D). Conventional combined resistance/endurance exercise training has limited efficacy to simultaneously improve muscle function and metabolism. We examined whether low-load blood-flow restriction training (BFRT) increases both muscle strength and mitochondrial oxidative capacity in T2D. Over 12 weeks, BFRT and conventional resistance training (CREST) similarly improved muscle strength despite lower workload in BFRT. Uniquely, BFRT enhanced muscle and adipose tissue oxidative capacity and increased muscle mitochondrial content. Transcriptomic profiling revealed more pronounced changes, particularly in angiogenesis-linked pathways, upon BFRT. BFRT also preferentially led to reductions in visceral adipose tissue volume and waist circumference, whereas CREST more effectively decreased subcutaneous adipose tissue volume. Both interventions lowered resting heart rate and diastolic blood pressure. These findings position BFRT as a promising low-load exercising strategy to simultaneously improve mitochondrial oxidative capacity, muscle strength, and body composition in individuals with T2D.

AIMS/HYPOTHESIS: Timely metabolic surgery improves glycaemic control and reduces cardiovascular risk for patients with type 2 diabetes. Young age is a known predictor of favourable metabolic outcome, but Roux-en-Y gastric bypass (RYGB) is often delayed owing to reported surgical and psychological risks in young adults. We hypothesised that use of RYGB in adults aged 18-35 years would result in higher rates of diabetes remission compared with older individuals, without an associated increase in morbidity. METHODS: We analysed prospective registry data from three expert centres where young adults (29.5±5 years) and older adults (48±6.8 years) (means ± SD) who were living with non-insulin-dependent type 2 diabetes underwent RYGB. Younger adults were matched in a 1:2 ratio to their older counterparts for duration of preoperative diabetes, sex, BMI and American Society of Anesthesiologists physical status score. The rates of diabetes remission and adverse events in both groups were compared five years postoperatively. RESULTS: A total of 79.1% (53/67) of the young adults and 76.9% (103/134) of the older adults attended the 5 year follow-up. Diabetes remission occurred earlier and more frequently in the young adult group, with an HR of 2.92 (95% CI 1.13, 7.59; p=0.027) and a median time to remission of 6 months (95% CI 3.1, 8.9), compared with 24 months (95% CI 10.9, 37.1) for older adults (p=0.001). There were no significant differences in all-cause adverse events, percentage weight change or loss to follow-up between groups. CONCLUSIONS/INTERPRETATION: Diabetes remission occurred earlier and more frequently in young adults within the first 5 years after RYGB. Surgical complications, nutritional deficiency or suboptimal weight loss were not different in the investigated young adult group compared with the older adults.