Research Radar
What is changing in GLP-1 science
Plain-English summaries of new clinical studies, FDA regulatory updates, medications in the pipeline, and telehealth policy. Updated as significant developments occur.
SURMOUNT-5 Results Published: Tirzepatide vs Semaglutide Head-to-Head for Weight Loss
Eli Lilly published full results from the SURMOUNT-5 trial, the first randomized controlled trial directly comparing tirzepatide and semaglutide head-to-head for weight loss in people without diabetes. At 72 weeks, participants taking tirzepatide lost an average of 20.2% of body weight compared to 13.7% for semaglutide — a difference of 6.5 percentage points. Both medications showed significant improvements in cardiovascular and metabolic markers. Gastrointestinal side effect rates were comparable between groups, with nausea being the most common adverse event for both medications. The study enrolled over 750 participants across multiple countries and used the highest approved doses for each medication. These results strengthen the evidence base for tirzepatide's dual GLP-1/GIP mechanism, but the study does not establish that one medication is appropriate for all patients — individual response, tolerability, and provider assessment remain central to treatment decisions.
FDA Issues Updated Guidance on GLP-1 Compounding
The FDA released updated draft guidance addressing compounded GLP-1 medications. Key points: the FDA emphasized that compounded products are not FDA-approved and have not been reviewed for safety, effectiveness, or quality. The guidance reiterated that compounding using bulk drug substances must comply with sections 503A and 503B of the FD&C Act. The FDA also stated it will prioritize enforcement action against compounders producing substandard or adulterated products, those making misleading claims about FDA approval, and those compounding copies of FDA-approved drugs. Patient advocacy groups noted the guidance provides some clarity but leaves many questions about access unresolved.
Retatrutide Phase 3 Results Expected Q4 2026: Triple Agonist Could Reshape the Landscape
Eli Lilly confirmed that top-line results from the TRIUMPH phase 3 clinical trial program for retatrutide — a triple agonist targeting GLP-1, GIP, and glucagon receptors — are expected in Q4 2026. Retatrutide generated significant attention after phase 2 results showed average weight loss of up to 24.2% at 48 weeks, the highest recorded for any pharmacological weight loss intervention. The phase 3 program is significantly larger, with multiple trials enrolling thousands of participants across varying BMI categories and health profiles. If phase 3 results confirm earlier findings, retatrutide could become the most effective weight loss medication available. However, the glucagon receptor agonism adds a new dimension — glucagon increases energy expenditure but also raises blood glucose, creating a complex risk-benefit profile. The FDA filing timeline depends on phase 3 outcomes, but industry analysts anticipate a potential approval decision in late 2027 or early 2028.
Orforglipron Advances: Oral Non-Peptide GLP-1 Shows Promising Phase 2 Data
Eli Lilly presented updated phase 2 data for orforglipron, an oral non-peptide GLP-1 receptor agonist that — unlike semaglutide oral (Rybelsus) — does not require fasting or specific timing around meals. At 36 weeks, the highest dose produced average weight loss of approximately 14.7%, which is competitive with injectable GLP-1 medications. The oral convenience factor is significant: orforglipron is a small molecule that can be taken with or without food, eliminating the fasting and timing restrictions that limit Rybelsus adherence. Gastrointestinal side effect rates were slightly higher than injectable GLP-1s but in line with what is expected from oral GLP-1 agonism. Phase 3 trials are underway (ACHIEVE program) with results expected in 2027. If approved, orforglipron could dramatically expand access to GLP-1 treatment by removing the injection barrier, which surveys indicate is a significant deterrent for a substantial minority of potential patients.
SELECT Trial Follow-Up: Semaglutide Cardiovascular Benefits Independent of Weight Loss Magnitude
A prespecified secondary analysis of the SELECT trial — which enrolled over 17,000 participants with cardiovascular disease and overweight/obesity but without diabetes — found that the cardiovascular benefits of semaglutide 2.4mg appeared early in treatment and were not fully explained by the amount of weight lost. Participants taking semaglutide experienced a 20% reduction in major adverse cardiovascular events compared to placebo. Notably, the reduction in cardiovascular events began within the first few months of treatment, before significant weight loss had occurred, suggesting that semaglutide may have direct cardiovascular protective effects beyond those mediated by weight reduction. The analysis controlled for weight loss magnitude and found that the cardiovascular benefit persisted even when accounting for differences in weight change between groups. These findings may influence how insurers and health systems evaluate the value of GLP-1 treatment, potentially supporting coverage decisions based on cardiovascular risk reduction rather than weight loss alone.
Medicare Part D GLP-1 Coverage Expansion: What Changed and Who Is Eligible
CMS finalized rules expanding Medicare Part D coverage for GLP-1 medications beyond diabetes indications. Under the new rules, Medicare Part D plans may cover GLP-1 medications for weight loss when prescribed for beneficiaries with a BMI of 30 or higher, or 27 or higher with at least one weight-related comorbidity. This represents a significant policy shift — historically, Medicare was prohibited by statute from covering weight loss medications. The change was enabled by new authority granted under recent legislation recognizing obesity pharmacotherapy as medically necessary treatment. However, coverage is not automatic: individual Part D plans retain formulary discretion, and prior authorization, step therapy, and quantity limits may apply. Beneficiaries should check their specific plan's formulary for coverage details. The rule also covers newer medications as they receive FDA approval for weight loss indications.
DEA Extends Telehealth Prescribing Flexibilities for Controlled Substances Through 2026
The DEA and HHS extended telehealth prescribing flexibilities for certain medications through December 31, 2026, while the agencies continue work on a permanent regulatory framework. This extension is relevant to the broader telehealth ecosystem: while GLP-1 medications themselves are not controlled substances, the telehealth infrastructure and provider-patient relationship standards shaped by these policies affect all telemedicine prescribing. The extension maintains the ability for providers to prescribe via telehealth without a prior in-person evaluation, a flexibility originally implemented during the COVID-19 public health emergency. Patient advocacy organizations and telehealth industry groups continue to push for a permanent framework that preserves telehealth access while addressing regulator concerns about appropriate prescribing. The outcome will shape how telemedicine platforms — including those prescribing GLP-1 medications — operate long-term.
New Study Examines GLP-1 Weight Loss and Bone Mineral Density
A prospective study published in JAMA Network Open examined bone mineral density changes in 195 postmenopausal women undergoing GLP-1-mediated weight loss over 12 months. Participants lost an average of 13.8% of body weight. Total hip bone mineral density decreased by approximately 1.5%, which was statistically significant but within the range observed with other weight loss methods. The study found that participants who engaged in regular resistance training preserved bone density more effectively than those who did not, and that adequate calcium and vitamin D intake was associated with smaller bone density declines. The authors concluded that while GLP-1 weight loss is associated with modest bone density reduction — consistent with the mechanical unloading that occurs with any significant weight loss — the clinical significance for fracture risk is uncertain and likely modifiable through resistance exercise and adequate nutrition. The study reinforces existing guidance about the importance of strength training and nutritional adequacy during GLP-1 treatment, particularly for postmenopausal women.
State-Level Compounding Pharmacy Legislation Tracker: 2026 Mid-Year Update
As of mid-2026, at least 14 states have introduced or passed legislation specifically addressing compounded GLP-1 medications, creating a patchwork of state-level regulations that supplement federal FDA oversight. Key developments: Texas passed SB 1422 requiring compounding pharmacies to disclose their state license status and FDA registration on all patient-facing materials. Florida enacted HB 789 establishing additional state-level quality testing requirements for compounded injectable medications, including sterility and potency verification. California's AB 2356, requiring compounding pharmacies to report adverse events to the state medical board, passed the Assembly and is pending in the Senate. Several other states have bills in committee addressing topics ranging from marketing restrictions to patient notification requirements. The regulatory trend is toward greater transparency and state-level oversight, which may affect how telehealth platforms and compounding pharmacies operate across different states.
FLOW Trial: Semaglutide Shows Kidney Protective Effects in People with Type 2 Diabetes
Novo Nordisk announced full results from the FLOW trial, which evaluated semaglutide's effect on kidney outcomes in over 3,500 participants with type 2 diabetes and chronic kidney disease. The trial was stopped early for efficacy after an interim analysis showed clear benefit. Participants receiving semaglutide 1.0mg experienced a 24% reduction in the composite primary endpoint of kidney failure, substantial loss of kidney function, or death from kidney or cardiovascular causes compared to placebo. The benefit was consistent across subgroups defined by baseline kidney function, age, sex, and concurrent medication use. The kidney benefit appeared to be partly independent of weight loss and blood sugar improvement, suggesting direct renal protective mechanisms of GLP-1 receptor activation. These findings expand the evidence base for GLP-1 medications beyond weight loss and glucose control, with potential implications for treatment guidelines and coverage decisions for people with kidney disease.