Dulaglutide research findings - The Echo Compendium

Dulaglutide MARKETED

Glycaemic control Decrease

High evidence

In AWARD-10, adding once-weekly dulaglutide to an SGLT2 inhibitor (with or without metformin) gave superior HbA1c reduction versus placebo at 24 weeks in inadequately...

Ludvik B, Frias JP, Tinahones FJ, et al. Dulaglutide as add-on therapy to SGLT2 inhibitor... Source

Full findingIn AWARD-10, adding once-weekly dulaglutide to an SGLT2 inhibitor (with or without metformin) gave superior HbA1c reduction versus placebo at 24 weeks in inadequately controlled type 2 diabetes.

PopulationAWARD-10: phase-3b, double-blind, placebo-controlled randomised trial, N=424; type 2 diabetes inadequately controlled on an SGLT2 inhibitor with or without metformin; dulaglutide 1.5/0.75 mg vs placebo; 24 weeks; NCT02597049.

Fundingindustry - Eli Lilly (trial sponsor; inferred from registration trial)

Scope limitsNET-NEW gather (WI-5). Dulaglutide on top of SGLT2i - the modern combination position. Observation only. Industry (Eli Lilly). Council interpretive review not yet run.

Comparatorsplacebo

Dulaglutide MARKETED

Glycaemic control Decrease

High evidence

In AWARD-3, dulaglutide monotherapy gave superior HbA1c reduction versus metformin monotherapy at 26 weeks in early type 2 diabetes.

Umpierrez G, Tofe Povedano S, Perez Manghi F, et al. Efficacy and safety of dulaglutide m... Source

PopulationAWARD-3: 52-week double-blind randomised trial, N=807; treatment-naive or low-dose-OAM type 2 diabetes (HbA1c 6.5-9.5%); subcutaneous dulaglutide 1.5/0.75 mg weekly vs metformin; primary endpoint 26 weeks.

Fundingindustry - Eli Lilly (trial sponsor; inferred from registration trial)

Scope limitsNET-NEW gather (WI-5). Defines dulaglutide-vs-metformin monotherapy glycaemic position. Observation only. Industry (Eli Lilly). Council interpretive review not yet run. funding_basis inferred-wrapper at gather; resolve to disclosed locator if load-bearing.

Comparatorsmetformin

Dulaglutide MARKETED

Glycaemic control Decrease

High evidence

In AWARD-5, dulaglutide 1.5 mg added to metformin gave greater HbA1c reduction than sitagliptin over 52 weeks; the Bayesian dose-finding portion selected 1.5 mg and...

Skrivanek Z, Gaydos BL, Chien JY, et al. Dose-finding results in an adaptive, seamless, r... Source

Full findingIn AWARD-5, dulaglutide 1.5 mg added to metformin gave greater HbA1c reduction than sitagliptin over 52 weeks; the Bayesian dose-finding portion selected 1.5 mg and 0.75 mg as the doses to carry forward.

PopulationAWARD-5: adaptive, seamless, double-blind randomised dose-finding plus confirmatory trial; type 2 diabetes on metformin; randomised 3:1:1 to seven dulaglutide doses, sitagliptin 100 mg, or placebo (placebo to 26 weeks, sitagliptin to 104 weeks); Bayesian adaptive randomisation.

Fundingindustry - Eli Lilly (trial sponsor; inferred from registration trial)

Scope limitsNET-NEW gather (WI-5). Dulaglutide-vs-sitagliptin (DPP-4i) glycaemic position plus the dose-selection rationale for the marketed 1.5/0.75 mg doses. This paper reports the dose-finding portion; the 104-week confirmatory AWARD-5 vs sitagliptin (Weinstock 2015) is a separate paper, not duplicated here. Observation only. Industry (Eli Lilly). Council interpretive review not yet run.

Comparatorssitagliptin; placebo

Dulaglutide MARKETED

Glycaemic control Decrease

High evidence

In AWARD-9, adding once-weekly dulaglutide 1.5 mg to titrated insulin glargine gave superior HbA1c reduction versus placebo plus glargine at 28 weeks, with concurrent...

Pozzilli P, Norwood P, Jodar E, et al. Placebo-controlled, randomized trial of the additi... Source

Full findingIn AWARD-9, adding once-weekly dulaglutide 1.5 mg to titrated insulin glargine gave superior HbA1c reduction versus placebo plus glargine at 28 weeks, with concurrent weight loss and a smaller required glargine dose increase.

PopulationAWARD-9: phase-3, double-blind, placebo-controlled randomised trial, N=300; type 2 diabetes inadequately controlled on titrated insulin glargine with or without metformin; dulaglutide 1.5 mg vs placebo added to glargine; 28 weeks; NCT02152371.

Fundingindustry - Eli Lilly (trial sponsor; inferred from registration trial)

Scope limitsNET-NEW gather (WI-5). Dulaglutide as add-on to basal insulin - a distinct clinical position. Carries both HbA1c and weight plus an insulin-sparing observation. Observation only. Industry (Eli Lilly). Council interpretive review not yet run.

Comparatorsplacebo

Dulaglutide MARKETED

Glycaemic control Decrease

High evidence

Once-weekly dulaglutide at 4.5 mg gave superior HbA1c reduction (approx -1.9%) and weight change (-4.7 kg) vs 1.5 mg (-1.5%, -3.1 kg) at 36 weeks in metformin-treated...

Frias JP et al. (AWARD-11), Diabetes Care 2021;44:765 Source

Full findingOnce-weekly dulaglutide at 4.5 mg gave superior HbA1c reduction (approx -1.9%) and weight change (-4.7 kg) vs 1.5 mg (-1.5%, -3.1 kg) at 36 weeks in metformin-treated T2D.

PopulationAWARD-11: T2D on metformin, randomised to dulaglutide 1.5/3.0/4.5 mg, 52 weeks (primary at 36 weeks)

Fundingindustry-Eli Lilly

Scope limitsMechanism: GLP-1(7-37) analogue linked to modified human IgG4 Fc (~5 day half-life, once-weekly). Marketed as Trulicity (T2D); approved US/EU. CV benefit in REWIND. No dedicated obesity (non-T2D) indication; weight is secondary. AWARD-11 identifiers are the established ones, reconfirm flag noted.

Comparatorsdulaglutide 1.5 mg; dulaglutide 3.0 mg

Dulaglutide MARKETED

Glycaemic control Decrease

Moderate evidence

In AWARD-1, once-weekly dulaglutide on background metformin plus pioglitazone gave superior HbA1c reduction versus both placebo and twice-daily exenatide at 26 weeks...

Wysham C, Blevins T, Arakaki R, et al. Efficacy and safety of dulaglutide added onto piog... Source

Full findingIn AWARD-1, once-weekly dulaglutide on background metformin plus pioglitazone gave superior HbA1c reduction versus both placebo and twice-daily exenatide at 26 weeks in type 2 diabetes.

PopulationAWARD-1: phase-3, multicentre, parallel-arm randomised trial (2:2:2:1), N=976; type 2 diabetes on metformin (1500-3000 mg) + pioglitazone (30-45 mg); 52 weeks (primary endpoint 26 weeks); comparators placebo (double-blind via double-dummy) and exenatide 10 ug twice daily (OPEN-LABEL active comparator). MIXED blinding: the dulaglutide-vs-placebo comparison is double-blind, the dulaglutide-vs-exenatide superiority comparison is open-label.

Fundingindustry - Eli Lilly (trial sponsor; inferred from registration trial)

Scope limitsopen-label (unblinded)

Comparatorsplacebo; exenatide

Dulaglutide MARKETED

Glycaemic control Decrease

Moderate evidence

In AWARD-6, once-weekly dulaglutide 1.5 mg was non-inferior to once-daily liraglutide 1.8 mg for HbA1c reduction at 26 weeks in metformin-treated type 2 diabetes.

Dungan KM, Povedano ST, Forst T, et al. Once-weekly dulaglutide versus once-daily liraglu... Source

PopulationAWARD-6: phase-3, randomised, open-label, parallel-group non-inferiority trial, N=599 (299 dulaglutide, 300 liraglutide); metformin-treated type 2 diabetes (HbA1c 7.0-10.0%); 26 weeks; NCT01624259.

Fundingindustry - Eli Lilly (trial sponsor; inferred from registration trial)

Scope limitsopen-label (unblinded)

Comparatorsliraglutide

Dulaglutide MARKETED

renal Decrease

Moderate evidence

REWIND exploratory renal composite reduced with dulaglutide versus placebo (albuminuria-driven; eGFR-decline/RRT components non-significant).

Gerstein HC et al. (REWIND renal), Lancet, 2019;394:131-138 Source

PopulationREWIND: N=9,901 T2D; median 5.4 years; exploratory analysis.

Fundingindustry - Eli Lilly and Company

Scope limitssurrogate/exploratory endpoint

Comparatorsplacebo

Dulaglutide MARKETED

renal Decrease

Moderate evidence

AWARD-7: dulaglutide slowed eGFR decline and reduced UACR versus insulin glargine at 52 weeks in T2D with moderate-to-severe CKD (parent-trial primary finding; the...

Am J Nephrol, 2023 (AWARD-7 fibrosis biomarkers) Source

Full findingAWARD-7: dulaglutide slowed eGFR decline and reduced UACR versus insulin glargine at 52 weeks in T2D with moderate-to-severe CKD (parent-trial primary finding; the captured paper reports fibrosis biomarkers).

PopulationAWARD-7 subset N=330 (dulaglutide 1.5 mg vs insulin glargine); T2D + moderate-to-severe CKD; 52 weeks; post hoc biomarker analysis.

Fundingindustry - Eli Lilly

Scope limitspost-hoc (not prespecified)

Comparatorsinsulin glargine; dulaglutide 0.75 mg

Dulaglutide MARKETED

renal Decrease

Moderate evidence

AWARD-7 exploratory analysis: dulaglutide 1.5 mg reduced the composite of >=40% eGFR decline or ESKD versus insulin glargine in T2D with moderate-to-severe CKD,...

Tuttle KR et al. (AWARD-7 exploratory), Kidney360 2020;2(2):254-262 Source

Full findingAWARD-7 exploratory analysis: dulaglutide 1.5 mg reduced the composite of >=40% eGFR decline or ESKD versus insulin glargine in T2D with moderate-to-severe CKD, concentrated in the macroalbuminuria subgroup; benefit at MATCHED glycaemia and BP argues for a glycaemia-independent renal effect.

PopulationAWARD-7 prespecified exploratory secondary analysis of a randomised controlled trial: dulaglutide 0.75/1.5 mg weekly vs daily insulin glargine; T2D + moderate-to-severe CKD (stage 3-4); 1 year; active comparator at matched glycaemia/BP.

Fundingindustry - Eli Lilly and Company (AWARD-7 sponsor; disclosed)

Scope limitsexploratory analysis (parent trial Tuttle 2018); active comparator insulin glargine at matched glycaemia/BP

Comparatorsinsulin glargine; dulaglutide 0.75 mg

Dulaglutide MARKETED

renal Mixed

Moderate evidence

AWARD-7 parent trial: in type 2 diabetes with moderate-to-severe CKD, dulaglutide gave HbA1c control non-inferior to insulin glargine with a slower decline in eGFR...

Tuttle KR, Lakshmanan MC, Rayner B, et al. Dulaglutide versus insulin glargine in patient... Source

Full findingAWARD-7 parent trial: in type 2 diabetes with moderate-to-severe CKD, dulaglutide gave HbA1c control non-inferior to insulin glargine with a slower decline in eGFR over 52 weeks.

PopulationAWARD-7: phase-3, multicentre, open-label, randomised trial, N=577; type 2 diabetes plus moderate-to-severe CKD (stages 3-4) on ACEi/ARB; dulaglutide 1.5/0.75 mg vs daily insulin glargine, both with insulin lispro; 52 weeks; NCT01621178.

Fundingindustry - Eli Lilly (trial sponsor; inferred from registration trial)

Scope limitsopen-label (unblinded)

Comparatorsinsulin glargine

Dulaglutide MARKETED

Weight change Decrease

High evidence

In AWARD-3, weight change with dulaglutide on a metformin-comparator monotherapy background was similar to metformin for the 1.5 mg dose and smaller (less loss) for...

Umpierrez G, Tofe Povedano S, Perez Manghi F, et al. Efficacy and safety of dulaglutide m... Source

Full findingIn AWARD-3, weight change with dulaglutide on a metformin-comparator monotherapy background was similar to metformin for the 1.5 mg dose and smaller (less loss) for 0.75 mg.

PopulationAWARD-3: 52-week double-blind randomised trial, N=807; early type 2 diabetes; dulaglutide 1.5/0.75 mg vs metformin monotherapy.

Fundingindustry - Eli Lilly (trial sponsor; inferred from registration trial)

Scope limitsNET-NEW gather (WI-5). Cleaner weight read than AWARD-1 (no pioglitazone) but comparator is metformin (weight-neutral/loss). Observation only; magnitude directional-from-abstract, full-text kg to be confirmed. Council interpretive review not yet run.

Comparatorsmetformin

Dulaglutide MARKETED

Weight change Decrease

High evidence

In AWARD-9, dulaglutide added to titrated insulin glargine produced weight loss whereas placebo plus glargine produced weight gain.

Pozzilli P, Norwood P, Jodar E, et al. Placebo-controlled, randomized trial of the additi... Source

PopulationAWARD-9: phase-3 double-blind placebo-controlled randomised trial, N=300; type 2 diabetes on titrated glargine; dulaglutide 1.5 mg vs placebo; 28 weeks.

Fundingindustry - Eli Lilly (trial sponsor; inferred from registration trial)

Scope limitsNET-NEW gather (WI-5). Weight benefit even on a weight-gaining insulin background; placebo-adjusted -2.41 kg confirmed exact from the abstract. Observation only. Council interpretive review not yet run.

Comparatorsplacebo

Dulaglutide MARKETED

Weight change Mixed

Moderate evidence

In AWARD-1 (type 2 diabetes on metformin plus pioglitazone), dulaglutide produced modest weight change against a weight-gaining background regimen, with the 1.5 mg...

Wysham C, Blevins T, Arakaki R, et al. Efficacy and safety of dulaglutide added onto piog... Source

Full findingIn AWARD-1 (type 2 diabetes on metformin plus pioglitazone), dulaglutide produced modest weight change against a weight-gaining background regimen, with the 1.5 mg dose giving near-neutral weight and 0.75 mg a small gain.

PopulationAWARD-1: phase-3 parallel-arm randomised trial, N=976; type 2 diabetes on metformin + pioglitazone; 52 weeks; comparators placebo (double-blind) and exenatide (OPEN-LABEL active comparator).

Fundingindustry - Eli Lilly (trial sponsor; inferred from registration trial)

Scope limitsopen-label (unblinded)

Comparatorsplacebo; exenatide

Dulaglutide MARKETED

Weight change Decrease

Moderate evidence

In AWARD-6, once-weekly dulaglutide 1.5 mg and once-daily liraglutide 1.8 mg produced broadly similar weight reduction over 26 weeks, with liraglutide numerically...

Dungan KM, Povedano ST, Forst T, et al. Once-weekly dulaglutide versus once-daily liraglu... Source

Full findingIn AWARD-6, once-weekly dulaglutide 1.5 mg and once-daily liraglutide 1.8 mg produced broadly similar weight reduction over 26 weeks, with liraglutide numerically slightly greater.

PopulationAWARD-6: phase-3 open-label non-inferiority trial, N=599; metformin-treated type 2 diabetes; dulaglutide 1.5 mg weekly vs liraglutide 1.8 mg daily; 26 weeks.

Fundingindustry - Eli Lilly (trial sponsor; inferred from registration trial)

Scope limitsopen-label (unblinded)

Comparatorsliraglutide

Thin or bounded evidence here means uncertainty remains visible. It is not evidence that an effect has been ruled out.

Dulaglutide MARKETED

Safety signals No change

High evidence

Short-term dulaglutide did not alter sexual desire or the reproductive axis in healthy lean men.

Dulaglutide on male sexual function and HPG axis (RCT), EBioMedicine 2024 Source

PopulationPeer-reviewed primary (women's-health wave)

Fundingacademic-Swiss National Science Foundation and Swiss foundations

Scope limitsA counter-pole AGAINST a direct libido effect (no weight-loss confound in lean men). Narrow: lean, eugonadal, 4 weeks. Pairs with the existing libido verdict.

Dulaglutide MARKETED

Safety signals Mixed

Moderate evidence

In a REWIND exploratory substudy, dulaglutide did NOT significantly reduce incident substantive cognitive impairment on the prespecified primary (unadjusted) analysis;...

Cukierman-Yaffe T, Gerstein HC, Colhoun HM, et al. Effect of dulaglutide on cognitive imp... Source

Full findingIn a REWIND exploratory substudy, dulaglutide did NOT significantly reduce incident substantive cognitive impairment on the prespecified primary (unadjusted) analysis; significance appeared only in a post-hoc baseline-score-adjusted analysis.

PopulationREWIND cognition substudy: N=8828 with baseline plus follow-up MoCA/DSST (of 9901); type 2 diabetes; double-blind placebo-controlled randomised trial; median 5.4 years; NCT01394952.

Fundingindustry - Eli Lilly (trial sponsor; inferred from registration trial)

Scope limitssurrogate/exploratory endpoint

Comparatorsplacebo

Thin or bounded evidence here means uncertainty remains visible. It is not evidence that an effect has been ruled out.

Dulaglutide MARKETED

Cardiovascular outcomes Decrease

High evidence

In T2D with a majority WITHOUT established CVD (primary-prevention-weighted), dulaglutide reduced MACE versus placebo, driven notably by reduced non-fatal stroke.

Gerstein HC et al. (REWIND), Lancet, 2019 Source

PopulationREWIND: N=9901; T2D, broad CV-risk (majority primary-prevention); double-blind placebo-controlled RCT; median 5.4 years (longest GLP-1 CVOT).

Fundingindustry - Eli Lilly

Scope limitsidentifier not fully verified

Comparatorsplacebo

Dulaglutide MARKETED

Cardiovascular outcomes Decrease

Moderate evidence

In a dedicated REWIND analysis, dulaglutide reduced total stroke, driven by ischaemic stroke, with no effect on haemorrhagic stroke and no change in post-stroke...

Gerstein HC, Hart R, Colhoun HM, et al. The effect of dulaglutide on stroke: an explorato... Source

Full findingIn a dedicated REWIND analysis, dulaglutide reduced total stroke, driven by ischaemic stroke, with no effect on haemorrhagic stroke and no change in post-stroke disability severity.

PopulationREWIND stroke analysis: N=9901 type 2 diabetes, broad CV risk; double-blind placebo-controlled randomised trial; median follow-up 5.4 years; NCT01394952.

Fundingindustry - Eli Lilly (trial sponsor; inferred from registration trial)

Scope limitssurrogate/exploratory endpoint

Comparatorsplacebo

Thin or bounded evidence here means uncertainty remains visible. It is not evidence that an effect has been ruled out.

Dulaglutide MARKETED

Gastrointestinal tolerability Increase

High evidence

Across the AWARD programme, dulaglutide's most common adverse events are gastrointestinal (nausea, diarrhoea, vomiting), dose-related and mostly mild-to-moderate and...

Ludvik B, Frias JP, Tinahones FJ, et al. Dulaglutide as add-on therapy to SGLT2 inhibitor... Source

Full findingAcross the AWARD programme, dulaglutide's most common adverse events are gastrointestinal (nausea, diarrhoea, vomiting), dose-related and mostly mild-to-moderate and transient, with low study-drug discontinuation.

PopulationAWARD programme phase-3 double-blind randomised trials: AWARD-10 (N=424, vs placebo, on SGLT2i) and the open-label AWARD-6 (N=599, vs liraglutide, on metformin); GI adverse-event incidence and discontinuation.

Fundingindustry - Eli Lilly (trial sponsor; inferred from registration trial)

Scope limitsNET-NEW gather (WI-5). Opens the dulaglutide tolerability-gi cell with a per-drug GI/discontinuation record (dulaglutide GI was previously inherited only via the SURPASS-CVOT comparator arm). AWARD-10 (placebo-controlled) and AWARD-6 (vs liraglutide) GI percentages confirmed from abstracts; AWARD-6 discontinuation 6%/6% confirmed. Observation only; the dose-relation of nausea (15% at 1.5 mg vs 5% at 0.75 mg in AWARD-10) is recorded as an observation. Industry (Eli Lilly). Council interpretive review not yet run.

Comparatorsplacebo; liraglutide

Dulaglutide MARKETED

Gastrointestinal tolerability No change

Moderate evidence

In the AWARD-6 head-to-head, study or study-drug discontinuation because of adverse events was the same for once-weekly dulaglutide and once-daily liraglutide.

Dungan KM, Povedano ST, Forst T, et al. Once-weekly dulaglutide versus once-daily liraglu... Source

PopulationAWARD-6: phase-3 open-label non-inferiority randomised trial, N=599; metformin-treated type 2 diabetes; dulaglutide 1.5 mg weekly vs liraglutide 1.8 mg daily; 26 weeks.

Fundingindustry - Eli Lilly (trial sponsor; inferred from registration trial)

Scope limitsopen-label (unblinded)

Comparatorsliraglutide

Thin or bounded evidence here means uncertainty remains visible. It is not evidence that an effect has been ruled out.

Dulaglutide MARKETED

heart-rate-chronotropy Increase

High evidence

Dulaglutide produces a small increase in pulse rate, consistent with the GLP-1 receptor agonist class, observed in the AWARD-5 dose-finding analysis.

Skrivanek Z, Gaydos BL, Chien JY, et al. Dose-finding results in an adaptive, seamless, r... Source

PopulationAWARD-5: adaptive double-blind randomised dose-finding trial; type 2 diabetes on metformin; pulse rate measured as a Bayesian dose-selection criterion vs placebo at 26 weeks.

Fundingindustry - Eli Lilly (trial sponsor; inferred from registration trial)

Scope limitsNET-NEW gather (WI-5). Opens the dulaglutide heart-rate-chronotropy cell with a per-drug record (previously inherited only via the SURPASS-CVOT comparator arm). The +0.78 bpm at 2.0 mg with a credible interval crossing zero is recorded faithfully - a small class-consistent chronotropic signal, not a large effect. Observation only; the 'why' open. Industry (Eli Lilly). Council interpretive review not yet run. funding_basis inferred-wrapper at gather; resolve to disclosed locator if load-bearing.

Comparatorsplacebo; sitagliptin

Thin or bounded evidence here means uncertainty remains visible. It is not evidence that an effect has been ruled out.

Dulaglutide MARKETED

Lipids and lipoproteins Decrease

Low evidence

In a small uncontrolled interventional pilot in adults with type 2 diabetes and verified atherosclerosis, dulaglutide treatment was followed by a significant reduction...

Hachula M, Kosowski M, Basiak M, Okopien B, Medicina (Kaunas) 2024;60(6):908 Source

Full findingIn a small uncontrolled interventional pilot in adults with type 2 diabetes and verified atherosclerosis, dulaglutide treatment was followed by a significant reduction in lipoprotein(a) [Lp(a)] and in the plaque-instability markers pentraxin-3 and MMP-9, while the conventional lipid fractions (LDL-C, triglycerides, non-HDL-C, HDL-C) did NOT change significantly.

PopulationUncontrolled single-arm interventional pilot (pre/post, no comparator, not randomised); N=34 adults (age 41-81, median 61) with type 2 diabetes, dyslipidaemia (88% on statins) and ultrasound-verified carotid atherosclerosis; dulaglutide 1.5-3 mg, 180 days.

Fundingacademic/independent analysis (manufacturer not study sponsor; per-study COI not individually audited)

Scope limitssmall sample (N~34)