COMPARATIVE EFFICACY AND SAFETY OF ORFORGLIPRON VS SGLT-2 INHIBITORS FOR THE TREATMENT OF INSUFFICIENTLY CONTROLLED TYPE 2 DIABETES AS AN ADD-ON TO BACKGROUND THERAPY OF 1-2 ORAL ANTIDIABETIC DRUGS: A NETWORK META-ANALYSIS
Author(s)
Alison Davie, BSc, MSc1, Tatjana Isailovic, PhD1, Jennifer Alyea, MPH, PhD1, Francesca Pannullo, PhD1, Andrew Briggs, DPhil2, Andrea Marcellusi, PhD3, Christophe De Block, PhD4.
1Eli Lilly and Company, Indianapolis, IN, USA, 2London School of Hygiene & Tropical Medicine, London, United Kingdom, 3University of Milan, Milano, Italy, 4Universitair Ziekenhuis Antwerpen, Antwerp, Belgium.
1Eli Lilly and Company, Indianapolis, IN, USA, 2London School of Hygiene & Tropical Medicine, London, United Kingdom, 3University of Milan, Milano, Italy, 4Universitair Ziekenhuis Antwerpen, Antwerp, Belgium.
OBJECTIVES: Orforglipron, a novel, once-daily oral non-peptide glucagon-like peptide-1 receptor agonist (GLP-1 RA) has been evaluated in insufficiently controlled type 2 diabetes (T2D). Direct evidence versus sodium-glucose co-transporter-2 inhibitors (SGLT-2i) are limited. This network meta-analysis (NMA) assessed the relative efficacy and safety of orforglipron versus SGLT-2i comparators. Data from the investigational capsule formulation (3mg, 12mg and 36mg) shown as equivalent tablet doses (2.5mg, 9mg and 17.2mg).
METHODS: A systematic literature review identified randomized controlled trials evaluating orforglipron or an SGLT-2i in adults with T2D receiving background therapy of 1-2 oral antidiabetic drugs (OAD) (predominantly metformin). Bayesian fixed- and random-effects NMAs were conducted with best fitting models selected. Outcomes included change from baseline in HbA1c, body weight, lipids, and blood pressure, and odds ratios for safety outcomes.
RESULTS: Thirty-two RCTs informed the NMA. Orforglipron demonstrated greater reductions in HbA1c versus SGLT-2i (95% credible intervals [CrI] excluding 0), consistent with clinically meaningful differences (~0.3-1.2%) and a dose dependent response. Doses of 9 and 17.2mg showed greater body weight reductions (~2.5-4.5kg), while 2.5mg showed smaller effects with 95% CrI including 0. Cardiometabolic risk factors (lipids and blood pressure) were broadly comparable, with favorable or similar reductions in total cholesterol and triglycerides at higher doses; LDL-C and HDL-C were similar (95% CrI including 0). The 17.2mg dose showed comparable or greater reductions in systolic blood pressure (~2-3mmHg). All doses showed similar odds of hypoglycemia versus SGLT-2i (95% CrI including 1). Higher odds of diarrhea were observed versus dapagliflozin 5 and 10mg, consistent with other GLP-1 RAs. Findings were consistent across sensitivity analyses and meta-regressions.
CONCLUSIONS: This NMA, which found dose-dependent greater glycemic and weight reductions and broadly comparable cardiometabolic risk-factor effects versus SGLT-2i, with safety findings generally consistent with other GLP-1 RAs, supports orforglipron as a potential oral option for T2D.
METHODS: A systematic literature review identified randomized controlled trials evaluating orforglipron or an SGLT-2i in adults with T2D receiving background therapy of 1-2 oral antidiabetic drugs (OAD) (predominantly metformin). Bayesian fixed- and random-effects NMAs were conducted with best fitting models selected. Outcomes included change from baseline in HbA1c, body weight, lipids, and blood pressure, and odds ratios for safety outcomes.
RESULTS: Thirty-two RCTs informed the NMA. Orforglipron demonstrated greater reductions in HbA1c versus SGLT-2i (95% credible intervals [CrI] excluding 0), consistent with clinically meaningful differences (~0.3-1.2%) and a dose dependent response. Doses of 9 and 17.2mg showed greater body weight reductions (~2.5-4.5kg), while 2.5mg showed smaller effects with 95% CrI including 0. Cardiometabolic risk factors (lipids and blood pressure) were broadly comparable, with favorable or similar reductions in total cholesterol and triglycerides at higher doses; LDL-C and HDL-C were similar (95% CrI including 0). The 17.2mg dose showed comparable or greater reductions in systolic blood pressure (~2-3mmHg). All doses showed similar odds of hypoglycemia versus SGLT-2i (95% CrI including 1). Higher odds of diarrhea were observed versus dapagliflozin 5 and 10mg, consistent with other GLP-1 RAs. Findings were consistent across sensitivity analyses and meta-regressions.
CONCLUSIONS: This NMA, which found dose-dependent greater glycemic and weight reductions and broadly comparable cardiometabolic risk-factor effects versus SGLT-2i, with safety findings generally consistent with other GLP-1 RAs, supports orforglipron as a potential oral option for T2D.
Conference/Value in Health Info
2026-11, ISPOR Europe 2026, Vienna, Austria
Value in Health, Volume 29, Issue 12S
Code
RWD158
Topic
Clinical Outcomes, Real World Data & Information Systems
Disease
Diabetes/Endocrine/Metabolic Disorders (including obesity)