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
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.