AWARD-7 deep-dive: dulaglutide vs insulin glargine in T2D with moderate-to-severe CKD
Last verified 2026-05-28 · Phase 3 · Completed (results published June 2018) · NCT01621178 ↗
AWARD-7 (NCT01621178) is the kidney-focused entry in the Assessment of Weekly AdministRation of LY2189265 in Diabetes (AWARD) program. Eli Lilly designed it to answer a question every other phase-3 GLP-1 trial of the era had sidestepped: does a once-weekly GLP-1 receptor agonist work as well as titrated basal insulin in patients with type 2 diabetes whose kidneys are already meaningfully impaired? Investigators randomized 577 adults with type 2 diabetes, HbA1c 7.5%-10.5%, and moderate-to-severe chronic kidney disease (eGFR ≥15 to <60 mL/min/1.73 m², stage 3a, 3b, or 4) 1:1:1 to once-weekly subcutaneous dulaglutide 1.5 mg, dulaglutide 0.75 mg, or daily insulin glargine titrated to a fasting plasma-glucose target, all on top of prandial insulin lispro at meals. The primary endpoint was change in HbA1c at week 26 with non-inferiority margins prespecified versus glargine, and the trial continued in blinded fashion through week 52 for secondary endpoints including eGFR slope, urinary albumin-to-creatinine ratio (UACR), body weight, and hypoglycemia rate. Results published by Tuttle and colleagues in The Lancet Diabetes & Endocrinology in August 2018 showed that both dulaglutide doses matched glargine on glycemic control while producing less kidney-function decline, lower albuminuria, weight loss instead of weight gain, and a sharp reduction in hypoglycemia.
- Enrollment
- 577
- Duration
- 52 weeks of double-blind treatment (primary HbA1c endpoint assessed at week 26; secondary kidney, weight, and hypoglycemia endpoints extended to week 52)
- Drug
- Dulaglutide (Trulicity) 1.5 mg and 0.75 mg
- Population
- Adults aged 18 or older with type 2 diabetes on insulin or insulin plus oral antihyperglycemic medication, HbA1c 7.5%-10.5%, BMI 23-45 kg/m², and presumed diabetic kidney disease (with or without hypertensive nephrosclerosis) at moderate-to-severe stage — eGFR ≥15 to <60 mL/min/1.73 m². Stage 5 CKD (eGFR <15) and dialysis were exclusions, as were rapidly progressing renal dysfunction, transplant history, type 1 diabetes, recent ketoacidosis or severe hypoglycemia, recent cardiovascular events, untreated proliferative retinopathy, and signs of pancreatitis. Baseline mean eGFR was approximately 38 mL/min/1.73 m² and mean HbA1c approximately 8.6%, reflecting an advanced-CKD population not typically enrolled in mainstream GLP-1 trials.
Primary endpoint
Change in HbA1c from baseline to week 26 (LS mean, MMRM)
Treatment arm
Dulaglutide 1.5 mg: −1.19% (SE 0.13); dulaglutide 0.75 mg: −1.12% (SE 0.12)
Comparator
Insulin glargine (titrated): −1.13% (SE 0.12)
Treatment difference: Mean difference vs glargine: dulaglutide 1.5 mg −0.05 percentage points (non-inferiority P<0.001); dulaglutide 0.75 mg +0.02 percentage points (non-inferiority P<0.001)
Both dulaglutide doses met the prespecified non-inferiority margin versus titrated insulin glargine for HbA1c reduction at week 26 in adults with moderate-to-severe CKD — a population in which most oral antihyperglycemics are contraindicated and insulin had been the default. Lead with the 1.5 mg arm: it is the labeled dose in AWARD-7 and the dose most clinicians use.
Secondary endpoints
| Endpoint | Treatment | Comparator | Difference |
|---|---|---|---|
| Change in HbA1c from baseline to week 52 (LS mean) The dulaglutide effect did not wane at 52 weeks despite no allowed up-titration, while glargine continued to be force-titrated to target. Roughly 33% of dulaglutide 1.5 mg participants reached HbA1c <7.0% at week 52 versus 29.1% on glargine. | Dulaglutide 1.5 mg: −1.10% (SE 0.13); dulaglutide 0.75 mg: −1.10% (SE 0.12) | Insulin glargine: −1.00% (SE 0.12) | Glycemic non-inferiority sustained through one year |
| Change in estimated glomerular filtration rate (eGFR, CKD-EPI) at week 52 The kidney-specific outcome that distinguished AWARD-7 from prior GLP-1 trials. eGFR slope was less negative on dulaglutide than on glargine despite equivalent glycemic control, suggesting a glucose-independent effect on kidney-function decline. Later analyses (Tuttle 2019 Diabetes Obes Metab, PMID 30762290) tied a portion of the eGFR preservation to dulaglutide-driven weight loss. | Dulaglutide 1.5 mg: −2.0 mL/min/1.73 m²; dulaglutide 0.75 mg: −1.5 mL/min/1.73 m² | Insulin glargine: −3.3 mL/min/1.73 m² | Smaller decline on both dulaglutide doses; difference vs glargine approximately +1.3 to +1.8 mL/min/1.73 m² at one year |
| Change in urinary albumin-to-creatinine ratio (UACR) at week 52 Albuminuria is the most validated near-term surrogate for kidney-outcome trials. The UACR reduction on dulaglutide 1.5 mg paralleled later signals in REWIND's renal exploratory composite and the AWARD-7 albuminuria subgroup analysis (Tuttle 2021 Kidney360, PMID 35373017) which found the benefit concentrated in participants with macroalbuminuria at baseline. | Dulaglutide 1.5 mg: −11.5%; dulaglutide 0.75 mg: −3.0% | Insulin glargine: +3.5% | Dulaglutide 1.5 mg lowered UACR while glargine raised it; the largest between-arm separation in any kidney biomarker reported |
| Change in body weight at week 52 Glargine's expected weight gain played out as predicted; dulaglutide produced modest sustained weight loss even in a CKD population that often struggles with anorexia, sarcopenia, and fluid shifts confounding the scale. | Dulaglutide 1.5 mg: −2.66 kg (SE 0.467); dulaglutide 0.75 mg: −1.71 kg (SE 0.448) | Insulin glargine: +1.57 kg (SE 0.429) | Between-arm difference approximately −4.2 kg on dulaglutide 1.5 mg vs glargine; weight moved in opposite directions |
| Total hypoglycemic-event rate over 52 weeks (events per patient-year, all categories combined) Hypoglycemia is the dominant safety harm of basal insulin in advanced CKD because impaired kidneys clear insulin slowly. The roughly two-thirds reduction in hypoglycemia rate is the load-bearing clinical case for choosing a GLP-1 over basal insulin in this population. | Dulaglutide 1.5 mg: 5.82 events/patient-year; dulaglutide 0.75 mg: 7.59 events/patient-year | Insulin glargine: 14.36 events/patient-year | Dulaglutide 1.5 mg cut total hypoglycemia rate by approximately 60% versus glargine |
| Severe hypoglycemia at week 52 (% of participants with ≥1 severe event) Severe hypoglycemia requires another person's assistance; in stage-3b/4 CKD it disproportionately drives emergency-department visits and falls. The signal is consistent with the broader hypoglycemia-rate finding and is the harm most likely to change prescriber behavior. | Dulaglutide 1.5 mg: 0%; dulaglutide 0.75 mg: 2.6% | Insulin glargine: 6.7% | Zero severe hypoglycemia events on the dulaglutide 1.5 mg arm versus 6.7% on glargine |
| HbA1c <7.0% (target attainment) at week 52 Both arms reached approximately one-third target attainment in a high-HbA1c CKD population. The clinically actionable finding is parity, not separation: a once-weekly injection achieved the same target rate as daily titrated insulin. | Dulaglutide 1.5 mg: 32.9%; dulaglutide 0.75 mg: 33.5% | Insulin glargine: 29.1% | Numerically higher on dulaglutide; differences modest |
| Change in serum creatinine at week 52 Serum creatinine is the input to eGFR, so the directionally consistent creatinine and eGFR readouts cross-check each other. The smaller creatinine rise on dulaglutide is what produces the less-negative eGFR slope. | Dulaglutide 1.5 mg: +0.07 mg/dL; dulaglutide 0.75 mg: +0.04 mg/dL | Insulin glargine: +0.12 mg/dL | Smaller rise in creatinine on both dulaglutide doses |
| Change in estimated creatinine clearance (eCrCl, Cockcroft-Gault) at week 52 An independent kidney-function estimator that does not rely on the CKD-EPI equation. The directional agreement with eGFR (CKD-EPI) makes the kidney-function signal harder to dismiss as an artifact of one filtration equation. | Dulaglutide 1.5 mg: −1.5 mL/min; dulaglutide 0.75 mg: −1.3 mL/min | Insulin glargine: −2.5 mL/min | Smaller decline on dulaglutide |
Adverse events
| Event | Treatment rate | Comparator rate |
|---|---|---|
| Nausea Most common GI adverse event on dulaglutide; consistent with the GLP-1 class profile. | Dulaglutide 1.5 mg: 19.8% (38/192); dulaglutide 0.75 mg: 14.2% (27/190) | Insulin glargine: 4.6% (9/194) |
| Diarrhoea | Dulaglutide 1.5 mg: 16.1% (31/192); dulaglutide 0.75 mg: 15.8% (30/190) | Insulin glargine: 7.2% (14/194) |
| Vomiting | Dulaglutide 1.5 mg: 13.5% (26/192); dulaglutide 0.75 mg: 8.4% (16/190) | Insulin glargine: 4.6% (9/194) |
| Constipation | Dulaglutide 1.5 mg: 6.3% (12/192); dulaglutide 0.75 mg: 5.3% (10/190) | Insulin glargine: 3.1% (6/194) |
| Decreased appetite Reported as an AE but partly a mechanism rather than a complication. | Dulaglutide 1.5 mg: 5.7% (11/192); dulaglutide 0.75 mg: 2.6% (5/190) | Insulin glargine: 1.5% (3/194) |
| Blood creatinine increased (laboratory AE) Laboratory-flagged creatinine rises were less common on dulaglutide; this is a safety-signal AE, not the kidney-outcome endpoint. | Dulaglutide 1.5 mg: 38.5% (74/192); dulaglutide 0.75 mg: 37.4% (71/190) | Insulin glargine: 46.4% (90/194) |
| Glomerular filtration rate decreased (laboratory AE) Investigator-reported eGFR-decline AEs were numerically lower on dulaglutide, consistent with the eGFR-endpoint result. | Dulaglutide 1.5 mg: 8.9% (17/192); dulaglutide 0.75 mg: 10.5% (20/190) | Insulin glargine: 13.4% (26/194) |
| Hyperkalaemia No excess hyperkalemia signal on dulaglutide despite the advanced-CKD population. | Dulaglutide 1.5 mg: 6.3% (12/192); dulaglutide 0.75 mg: 4.2% (8/190) | Insulin glargine: 6.7% (13/194) |
| Urinary tract infection | Dulaglutide 1.5 mg: 6.8% (13/192); dulaglutide 0.75 mg: 5.3% (10/190) | Insulin glargine: 9.8% (19/194) |
| Anaemia Anemia of CKD; lower incidence on dulaglutide, possibly reflecting slower eGFR decline. | Dulaglutide 1.5 mg: 2.6% (5/192); dulaglutide 0.75 mg: 1.6% (3/190) | Insulin glargine: 5.2% (10/194) |
| Serious adverse events (any) Overall SAE rates favored dulaglutide; no organ-system clustering of concern. | Dulaglutide 1.5 mg: 21.4% (41/192); dulaglutide 0.75 mg: 25.3% (48/190) | Insulin glargine: 28.9% (56/194) |
Clinical significance
AWARD-7 was the first phase-3 trial to put a GLP-1 receptor agonist head-to-head against the established standard of care — titrated basal insulin — in adults with type 2 diabetes whose kidneys were already meaningfully impaired. The trial answered three questions simultaneously: dulaglutide matches insulin glargine on HbA1c reduction even in advanced CKD, it preserves kidney function better than glargine over a year, and it cuts hypoglycemia rates by roughly two-thirds (and severe hypoglycemia to essentially zero on the 1.5-mg dose). The eGFR and UACR signals foreshadowed the dedicated kidney-outcome trials that followed: REWIND's exploratory renal composite, the FLOW primary kidney composite for semaglutide, and ongoing trials of tirzepatide and dual agonists in CKD. AWARD-7 is the reason most modern guidelines list GLP-1 receptor agonists as preferred over basal insulin for glycemic management in stage 3-4 CKD when intensification is needed.
Frequently asked questions
Why use dulaglutide instead of insulin in advanced chronic kidney disease?
AWARD-7 showed that dulaglutide 1.5 mg matched titrated insulin glargine on HbA1c reduction at both 26 and 52 weeks while producing less decline in estimated glomerular filtration rate (−2.0 vs −3.3 mL/min/1.73 m² over 52 weeks), lower urinary albumin-to-creatinine ratio (−11.5% vs +3.5%), modest weight loss instead of weight gain (−2.66 kg vs +1.57 kg), and a roughly 60% reduction in total hypoglycemic events (5.82 vs 14.36 events per patient-year). Severe hypoglycemia, the harm most likely to drive an emergency-department visit in CKD, occurred in 0% of the dulaglutide 1.5 mg arm versus 6.7% on glargine. The bundle of equivalent glycemic control, kidney-function preservation, weight loss, and dramatically lower hypoglycemia is the clinical case for choosing dulaglutide over basal insulin when intensification is needed in stage 3a-4 CKD.
How does AWARD-7 compare with the FLOW trial?
AWARD-7 (Tuttle 2018, PMID 29910024) was a 52-week glycemic non-inferiority trial of dulaglutide versus insulin glargine in 577 adults with type 2 diabetes and moderate-to-severe CKD; kidney biomarkers (eGFR slope, UACR) were secondary endpoints. FLOW (Perkovic 2024, PMID 38785209) was a 3,533-participant event-driven phase-3b trial of semaglutide 1.0 mg versus placebo with a hard kidney composite (kidney failure, sustained ≥50% eGFR decline, or kidney or cardiovascular death) as the primary endpoint — the first GLP-1 trial powered for a kidney outcome. AWARD-7 generated the eGFR-slope and UACR signal that helped justify dedicated kidney-outcome programs; FLOW delivered the registrational kidney-composite proof and produced the January 2025 FDA Ozempic label expansion for kidney-disease progression in type 2 diabetes.
Was hypoglycemia really that much lower on dulaglutide?
Yes. The total hypoglycemic-event rate over 52 weeks was 5.82 events per patient-year on dulaglutide 1.5 mg and 7.59 on dulaglutide 0.75 mg versus 14.36 on insulin glargine — a 59% reduction with the labeled 1.5-mg dose. Documented symptomatic hypoglycemia rate was 4.44 versus 9.62 events per patient-year. Severe hypoglycemia occurred in 0% of the dulaglutide 1.5 mg group versus 6.7% on glargine. The mechanism is straightforward: GLP-1 receptor agonists raise insulin secretion only in response to elevated glucose, so they do not drive plasma glucose below normal the way fixed-dose basal insulin can in patients whose impaired kidneys are clearing insulin slowly. In advanced CKD, where hypoglycemia is the dominant safety risk of insulin therapy, that mechanistic difference translates into a roughly two-thirds reduction in total events.
What does the eGFR-slope finding mean clinically?
Over 52 weeks of treatment, eGFR fell by 2.0 mL/min/1.73 m² on dulaglutide 1.5 mg and 1.5 mL/min/1.73 m² on dulaglutide 0.75 mg versus 3.3 mL/min/1.73 m² on insulin glargine — a between-arm difference of roughly 1.3 to 1.8 mL/min/1.73 m² over one year. In a CKD population already at stage 3a-4, that is the difference between losing a typical year of kidney function and losing roughly half of it. AWARD-7 was not powered for a hard kidney-failure outcome, so the eGFR-slope finding is a surrogate signal, not a registrational kidney endpoint. But the direction and magnitude were consistent with REWIND's renal composite and helped motivate the FLOW trial, which converted that signal into a 24% reduction in major kidney-disease events with semaglutide. A follow-up analysis (Tuttle 2019 Diabetes Obes Metab, PMID 30762290) attributed part of the eGFR preservation to dulaglutide-driven weight loss.
Should dialysis patients use GLP-1 receptor agonists based on AWARD-7?
No — AWARD-7 explicitly excluded participants on dialysis and those with stage-5 CKD (eGFR <15 mL/min/1.73 m²). The enrolled population had eGFR 15 to <60 mL/min/1.73 m², covering stage 3a, 3b, and 4 CKD. The dulaglutide US prescribing information was updated based on AWARD-7 to indicate that no dose adjustment is required across this eGFR range, but no efficacy or safety claim was made for dialysis-dependent patients. Smaller pharmacokinetic studies and some real-world series have explored GLP-1 use in hemodialysis since 2018, but the evidence base remains thin and AWARD-7 cannot be extrapolated to that setting. Dialysis-dependent patients on insulin who are candidates for a GLP-1 should be managed with input from nephrology, with hypoglycemia monitoring and gradual titration.
Did AWARD-7 change how guidelines treat type 2 diabetes in CKD?
Yes. AWARD-7 was one of the earliest randomized datasets demonstrating that a GLP-1 receptor agonist could provide equivalent glycemic control to insulin in advanced CKD with less hypoglycemia, weight loss instead of weight gain, and signals of kidney-function preservation. Subsequent guideline updates from the American Diabetes Association, KDIGO (Kidney Disease: Improving Global Outcomes), and the American Association of Clinical Endocrinology positioned GLP-1 receptor agonists as preferred over basal insulin for glycemic intensification in patients with type 2 diabetes and CKD stage 3 or higher, particularly when weight management or hypoglycemia avoidance are priorities. The dulaglutide US prescribing information cites AWARD-7 as the evidence base for use across the eGFR range studied. Later trials including REWIND and FLOW reinforced and extended the cardiovascular and kidney-outcome case.
References
- 1.Tuttle KR, Lakshmanan MC, Rayner B, Busch RS, Zimmermann AG, Woodward DB, Botros FT. Dulaglutide versus insulin glargine in patients with type 2 diabetes and moderate-to-severe chronic kidney disease (AWARD-7): a multicentre, open-label, randomised trial. Lancet Diabetes Endocrinol. 2018. PMID: 29910024.
- 2.U.S. National Library of Medicine. AWARD-7: A Study Comparing Dulaglutide With Insulin Glargine on Glycemic Control in Participants With Type 2 Diabetes (T2D) and Moderate or Severe Chronic Kidney Disease (CKD) — Study Results. ClinicalTrials.gov, NCT01621178. 2017. https://clinicaltrials.gov/study/NCT01621178
- 3.Tuttle KR, Rayner B, Lakshmanan MC, Kwan AYM, Konig M, Shurzinske L, Botros FT. Body weight and eGFR during dulaglutide treatment in type 2 diabetes and moderate-to-severe chronic kidney disease (AWARD-7). Diabetes Obes Metab. 2019. PMID: 30762290.
- 4.Tuttle KR, Rayner B, Lakshmanan MC, Kwan AYM, Konig M, Shurzinske L, Botros FT. Clinical Outcomes by Albuminuria Status with Dulaglutide versus Insulin Glargine in Participants with Diabetes and CKD: AWARD-7 Exploratory Analysis. Kidney360. 2021. PMID: 35373017.