Safety of a remote disease management program to improve sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists prescribing in type 2 diabetes with elevated cardiovascular or kidney risk

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.