GLP-1 Share by Indication

Approximate 2025 to 2026 US prescription share within each indication, by primary molecule. T2D and obesity carry the most measurement weight. CV (Wegovy March 2024), OSA (Zepbound December 2024), CKD (semaglutide January 2025), and adolescent (Wegovy 2022) are single-molecule indications today; the tirzepatide MACE label expansion expected H1 2026 will split the CV row.

Approximate 2025 to 2026 US prescription share within each indication. T2D and obesity carry the most weight; CV (semaglutide-only via Wegovy approval March 2024), OSA (tirzepatide-only via Zepbound approval December 2024), CKD (semaglutide-only via January 2025 approval), and adolescent (Wegovy-only since December 2022) are single-molecule today. Tirzepatide MACE label expansion (expected H1 2026) and Zepbound adolescent expansion (late 2026) will split the CV and adolescent rows.

T2D: A1c Reduction Across Pivotal Trials

Mean A1c reduction (percentage points) in pivotal T2D trials. Tirzepatide leads at every dose level (~2.5 pp at the 15mg arm); SURPASS-2 directly compared tirzepatide vs semaglutide 1mg. Oral semaglutide (PIONEER) modestly trails injectable; dulaglutide and liraglutide anchor the lower end.

Mean A1c reduction (percentage points) in pivotal T2D trials. Tirzepatide leads at every dose level, with the 15mg arm achieving ~2.5 pp A1c reduction. SURPASS-2 directly compared tirzepatide vs semaglutide 1mg; subsequent trials anchor the rest. Oral semaglutide (PIONEER) modestly trails injectable. Older agents (dulaglutide, liraglutide) anchor the lower end of the class.

Obesity: Placebo-Adjusted Weight Loss

Pivotal and Phase 2 obesity trials ranked by placebo-adjusted weight loss, color-coded by mechanism. Triple agonists (retatrutide) and dual GLP-1/GIP combos (CT-388, tirzepatide) lead. Trial durations vary from 13 to 72 weeks; shorter trials may understate maximum efficacy.

Placebo-adjusted weight loss across pivotal and Phase 2 obesity trials, color-coded by mechanism. Triple agonists (retatrutide) and dual GLP-1/GIP combos (CT-388, tirzepatide) lead; oral non-peptide (orforglipron) lags injectables but offers patient-preference upside. Trial durations vary (13 to 72 weeks); shorter trials may understate maximum efficacy. The 22.7% CagriSema figure cites the Phase 3a NEJM headline value.

SELECT: MACE Reduction in CVD + Overweight/Obesity

SELECT (NEJM 2023) randomized 17,604 patients with established CVD plus overweight/obesity (no diabetes) to semaglutide 2.4mg vs placebo. The 20% primary MACE reduction triggered Wegovy's March 2024 cardiovascular label expansion and the CMS GLP-1 Bridge program logic.

Endpoint	HR	95% CI	Reduction
MACE (CV death + non-fatal MI + non-fatal stroke)	0.80	0.72 to 0.90	20%
Non-fatal myocardial infarction	0.72	0.61 to 0.85	28%
Cardiovascular death	0.85	0.71 to 1.01	15%
Non-fatal stroke	0.93	0.74 to 1.15	7%
All-cause mortality	0.81	0.71 to 0.93	19%
Heart failure composite	0.82	0.71 to 0.96	18%

SELECT (NEJM 2023) randomized 17,604 patients with established CVD plus overweight/obesity (no diabetes) to semaglutide 2.4mg vs placebo over 39.8 months mean follow-up. The 20% primary MACE reduction triggered Wegovy's March 2024 cardiovascular label expansion and the subsequent CMS GLP-1 Bridge program logic for Medicare beneficiaries with covered CV indications. Non-fatal MI showed the strongest individual signal (28% reduction). Stroke was directionally favorable but not statistically significant on its own.

FLOW: Kidney Outcomes in T2D + CKD

FLOW (NEJM 2024) randomized 3,533 patients with T2D plus CKD to semaglutide 1mg vs placebo over 3.4-year median follow-up. The 24% reduction in the primary composite endpoint led to FDA approval for semaglutide CKD in January 2025.

Endpoint	HR	95% CI	Reduction
Primary composite (kidney failure + sustained 50% eGFR loss + kidney/CV death)	0.76	0.66 to 0.88	24%
Kidney-specific composite	0.79	0.66 to 0.94	21%
Cardiovascular events (MACE)	0.82	0.68 to 0.98	18%
All-cause mortality	0.80	0.67 to 0.95	20%
Annual eGFR slope (mL/min/1.73m2/yr) Improvement in slope (less decline) vs placebo	1.16	0.86 to 1.47	16%

FLOW (NEJM 2024) randomized 3,533 patients with T2D plus CKD to semaglutide 1mg vs placebo over 3.4-year median follow-up. The primary composite endpoint (kidney failure, sustained 50% eGFR loss, kidney death, or CV death) was reduced 24%. Cardiovascular events and all-cause mortality also dropped. FDA approval for semaglutide CKD followed in January 2025, opening a Medicare Part D-covered indication.

SURMOUNT-OSA: Tirzepatide AHI Reduction in Obese OSA

SURMOUNT-OSA (NEJM 2024) randomized 469 patients to tirzepatide vs placebo over 52 weeks across two parallel studies. Both studies showed dramatic AHI reduction on tirzepatide. FDA approval for Zepbound for moderate-to-severe OSA in obesity followed in December 2024.

SURMOUNT-OSA (NEJM 2024) randomized 469 obese patients with moderate-to-severe OSA to tirzepatide vs placebo over 52 weeks. Both parallel studies (without PAP at baseline, and with PAP) showed dramatic AHI reduction on tirzepatide (-25.3 and -29.3 events/hour) versus placebo (-5.3 and -5.5). FDA approval for Zepbound for moderate-to-severe OSA in obesity followed in December 2024, opening sleep medicine and pulmonology as new prescriber bases.

MASH: Fibrosis Improvement and MASH Resolution by Mechanism

Paired histology endpoints across the main MASH agents. Resmetirom (Madrigal Rezdiffra) is the only FDA-approved option (March 2024). Semaglutide (ESSENCE) and efruxifermin (Akero, acquired by Novo $5.2B late 2025) post stronger headline rates with different patient mix. Pemvidutide IMPACT pivotal 2026.

Paired histology endpoints (fibrosis improvement without MASH worsening, and MASH resolution without fibrosis worsening) across the main MASH agents. Resmetirom (Madrigal Rezdiffra) is the only FDA-approved option to date (March 2024). Semaglutide (ESSENCE Phase 3) and efruxifermin (Akero, acquired by Novo for $5.2B late 2025) post stronger headline rates but had different patient mix and longer follow-up. Pemvidutide IMPACT pivotal readout in 2026 will add the GLP-1/glucagon dual to the comparison.

Pediatric and Adolescent (ages 12 to 17)

STEP TEENS (NEJM 2022) drove Wegovy adolescent approval in December 2022; remains the only currently-approved adolescent GLP-1. Zepbound adolescent late-stage trials read out 2026. Lilly is also studying tirzepatide down to age 6. AAP guidelines (January 2023) recommend GLP-1 from age 12.

Mean placebo-adjusted body weight reduction in adolescent obesity trials. STEP TEENS (NEJM 2022): semaglutide 2.4mg in 12 to 17 year olds achieved 16.1% weight loss vs 0.6% placebo. Wegovy adolescent approval was December 2022; remains the only currently-approved adolescent GLP-1. Zepbound adolescent late-stage trials read out 2026. Lilly is also studying tirzepatide down to age 6. AAP guidelines (January 2023) recommend GLP-1 from age 12 with co-management of weight-related comorbidities.

Emerging Indications Pipeline

Indications beyond the seven covered above where GLP-1 has material trial activity. The most consequential near-term readout is Alzheimer's (semaglutide EVOKE Phase 3, 2026). Addiction has observational support but no near-term FDA pathway. HFpEF data exists but rolls under the CV label. Mortality benefits in non-CVD populations are the long-tail story tracked by reinsurers.

Indication	Trial	Sponsor	Readout	Rationale
Alzheimer's disease	EVOKE / EVOKE+ (semaglutide 2.4mg, Phase 3)	Novo Nordisk	2026	Earlier liraglutide trials showed slowed brain shrinkage; EVOKE tests if semaglutide slows cognitive decline in early Alzheimer's.
Alcohol use disorder (AUD)	Multiple Phase 2 trials	NIH-NIAAA + investigator-initiated	2026 to 2027	Observational data suggests 44 to 75% reduction in drinking. Endocrine Society 2025 review and emerging Phase 2 data; FDA AUD label expansion not yet a near-term goal.
Opioid use disorder (OUD)	Phase 1 and 2 investigator trials	NIH-NIDA + academic	2027+	Receptor overlap with reward circuits. Preclinical and early human data support continued investigation.
Parkinson's disease	Multiple Phase 2 (exenatide, lixisenatide)	Academic + NIH	2026 to 2027	Mixed Phase 2 data; some signals of disease-modifying effect on motor scores.
Heart failure (HFpEF)	STEP-HFpEF (sema, published); SUMMIT (tirz, published)	Novo Nordisk; Eli Lilly	Published 2024	Both showed symptom improvement and exercise capacity. Not yet a separate FDA indication; covered under CV label.
Polycystic ovary syndrome (PCOS)	Phase 2 investigator + off-label use	Academic	2027+	Weight loss and insulin sensitivity improvements drive demand; no near-term FDA filing planned.
Mortality in non-CVD populations	Real-world cohort studies (Truveta, claims)	Reinsurers + academic	Continuous	Swiss Re projects up to 6.4% US mortality reduction by 2045; Munich Re notes 0.2 to 0.5% annual mortality improvement contingent on adherence.

Indications beyond T2D, obesity, CV, OSA, CKD, MASH, and pediatric where GLP-1 has material trial activity. The most consequential near-term readout is Alzheimer's (semaglutide EVOKE Phase 3, 2026). Addiction (alcohol, opioid) has strong observational data but no near-term FDA filing pathway. HFpEF (STEP-HFpEF, SUMMIT) shows symptom improvement but is covered under the broader CV label rather than a separate indication. Mortality benefits in non-CVD populations are the long-tail story tracked by reinsurers (Swiss Re, Munich Re).