HARMONY OUTCOMES: A Win for a Withdrawn Drug
Last verified May 2026 · Phase 3 in substance, logged on the registry as Phase 4 because it ran after approval as a cardiovascular outcomes study · Finished and published October 2018 — three months after GSK had already pulled the drug from every market worldwide, for commercial reasons rather than anything to do with safety · NCT02465515 ↗
Albiglutide never sold well. It was less potent than its competitors on both glucose and weight, and by 2017 GSK had decided it was not worth continuing. The outcomes trial was already running and completed anyway, which is how a drug nobody can buy came to hold one of the larger cardiovascular results in its class. The median follow-up of 1.6 years is short by the standards of these trials, which usually makes a positive finding harder rather than easier to obtain.
- Enrollment
- 9,463
- Duration
- A median 1.6 years. The trial ran until enough events accumulated: the committee judged the threshold met in November 2017, and the last participant visit was March 12, 2018
- Drug
- Albiglutide 30-50 mg weekly (subcutaneous)
- Population
- Adults 40 and over whose type 2 diabetes came with existing cardiovascular disease — an event in the heart, brain or limb arteries, or a procedure to repair one — with an HbA1c of at least 7.0% on stable treatment. ★ This is a pure secondary-prevention population, not a mixture, which makes it easier to read than most trials in this class. Average age 64.1, 30.7% women, average BMI 32.3, average HbA1c 8.7%, and nearly 14 years since diagnosis. Roughly 70% had had a heart attack or a coronary procedure, about 18% a stroke.
Primary endpoint
Cardiac death, a nonfatal heart attack, or a nonfatal stroke — whichever came first
Treatment arm
338 of 4,731 (7%) — incidence rate 4.6 events per 100 person-years
Comparator
428 of 4,732 (9%) — incidence rate 5.9 events per 100 person-years
Treatment difference: Hazard ratio 0.78 (95% CI 0.68–0.90); P<0.0001 for non-inferiority; P=0.0006 for superiority
★ A 22% reduction, among the strongest in this class, achieved in a shorter trial than any of its peers — and short follow-up normally makes a positive result harder to reach, not easier. Roughly 2 percentage points in absolute terms.
Secondary endpoints
| Endpoint | Treatment | Comparator | Difference |
|---|---|---|---|
| Death from a cardiac cause ⚠ Lower, but not significantly. At 1.6 years there is simply not enough time for deaths to separate — which is the main cost of how quickly this trial finished. | Incidence rate 1.61 events per 100 person-years on albiglutide | Incidence rate 1.72 events per 100 person-years on placebo | Hazard ratio approximately 0.93 (95% CI crossed 1.0); no significant reduction |
| Heart attacks that were not fatal ★ Down 25%, and the biggest single contributor to the headline. ⚠ Note that this is the opposite of the semaglutide trial, where strokes carried the benefit and heart attacks barely moved. Same class, different fingerprints. | Incidence rate 2.43 events per 100 person-years on albiglutide | Incidence rate 3.26 events per 100 person-years on placebo | Hazard ratio 0.75 (95% CI 0.61–0.90); statistically significant |
| Strokes that were not fatal Fewer, without reaching significance — the exact inverse of semaglutide's pattern, and part of why claims about this class need to name a drug. | Incidence rate 1.25 events per 100 person-years on albiglutide | Incidence rate 1.45 events per 100 person-years on placebo | Hazard ratio approximately 0.86; confidence interval crossed 1.0 |
| The same count plus emergency procedures to reopen an artery Tracked the headline closely, suggesting the benefit on heart attacks extended to the emergencies that precede them. | Incidence rate 5.06 events per 100 person-years on albiglutide | Incidence rate 6.45 events per 100 person-years on placebo | Hazard ratio 0.78 (95% CI 0.69–0.89); statistically significant |
| Cardiac death or admission for heart failure ⚠ Pointing the right way and not significant. Heart failure has been a persistent null across this whole class, and it is where SGLT2 inhibitors clearly outperform. | Incidence rate 2.49 events per 100 person-years on albiglutide | Incidence rate 2.92 events per 100 person-years on placebo | Hazard ratio approximately 0.85; confidence interval crossed 1.0 |
| Serious small-vessel damage: needing dialysis or a transplant, going blind from diabetes, or needing eye injections or laser Numerically fewer — the trial was never sized to prove this, but the direction matches the kidney and eye signals seen with other drugs in the class. | Incidence rate 0.46 events per 100 person-years on albiglutide | Incidence rate 0.69 events per 100 person-years on placebo | Hazard ratio approximately 0.66; confidence interval crossed 1.0 |
| Three-month average blood sugar at 16 months ★ The most revealing row here. This drug was a weak glucose-lowerer — about half a point better than placebo from a starting HbA1c of 8.7% — and it still produced one of the larger cardiac reductions in the class. Whatever protects the heart, it is not the blood sugar. | −0.83 percentage points (least-squares mean) on albiglutide | −0.31 percentage points (least-squares mean) on placebo | Estimated treatment difference approximately −0.5 percentage points vs placebo |
| Weight change at 16 months ⛔ Under 1 kg against placebo. This molecule is fused to albumin and barely reaches the brain, which likely explains both the negligible weight effect and the weak appetite suppression. Nothing here is relevant to the weight drugs sold today. | −1.36 kg (least-squares mean) on albiglutide | −0.53 kg (least-squares mean) on placebo | Estimated treatment difference approximately −0.8 kg vs placebo |
| How long before someone not already on insulin had to start it ★ Buried at publication and worth surfacing: the rate of starting insulin was less than half that on placebo. For a patient, avoiding insulin is a concrete quality-of-life outcome, and it got no attention because the cardiac headline took the room. | Incidence rate 3.56 events per 100 person-years on albiglutide | Incidence rate 8.58 events per 100 person-years on placebo | Hazard ratio approximately 0.42; statistically significant |
| Hitting an HbA1c of 7% or under without a severe low and without gaining weight 26.0% managed all three at once against 15.1% on placebo. ★ This combination — target blood sugar, no dangerous lows, no weight gain — is what older diabetes drugs could rarely deliver together, and it is the everyday case for this class separate from anything about hearts. | 26.0% of participants on albiglutide | 15.1% of participants on placebo | Treatment difference approximately +11 percentage points; statistically significant |
Adverse events
| Event | Treatment rate | Comparator rate |
|---|---|---|
| Pancreatitis, confirmed by independent review No meaningful excess, on small numbers, matching the other large trials in this class. | 0.2% (10/4,731) | 0.1% (7/4,732) |
| Pancreatic cancer No imbalance between the arms over the trial period. | 0.1% (6/4,731) | 0.1% (5/4,732) |
| Medullary thyroid cancer ★ Not one case among 9,463 people. This is the cancer behind the boxed warning on the whole class, and that warning comes from rodent studies rather than any human trial. | 0 of 4,731 | 0 of 4,732 |
| Reactions where the injection went in ⚠ The most common problem attributable to the drug, and worse than its competitors — prescribers cited it as a reason the product never caught on. | Higher on albiglutide than on placebo (numerically the most common drug-attributable adverse event) | Lower on placebo |
| Deaths judged related to treatment Two on the drug against three on placebo, assessed by investigators who did not know which arm anyone was in. | 2 of 4,731 (<1%) | 3 of 4,732 (<1%) |
| Stopped the drug over a side effect ★ Comparable to placebo — an easier drug to stay on than semaglutide or liraglutide, and for the same reason it was weaker: less pharmacological punch means less nausea. | Comparable to placebo overall | Comparable to albiglutide overall |
Subgroup analyses
- People who had already had a heart attack or a coronary procedure — about 70%: In line with the trial overall
The dominant group, and the one that defines who this evidence applies to.
- People who had already had a stroke — about 18%: The same direction, with wider uncertainty on smaller numbers
⚠ Not enough participants to reach a conclusion on its own.
- Participants 65 and over — roughly half the trial: The same benefit as everyone else
No age effect across any of the pre-planned cut points.
- People whose blood sugar started higher or lower than the trial median: The same benefit either way
★ More evidence that the cardiac protection does not run through glucose — a drug with a small blood-sugar effect helped people whose blood sugar was already lower just as much.
Clinical significance
The value here is entirely to the class argument: another structurally distinct GLP-1 reducing cardiovascular events strengthens the case that this is a mechanism effect rather than a property of one or two molecules. ⚠ It also complicates the simple story, because EXSCEL tested exenatide in a larger and longer trial and came back neutral. Any claim that GLP-1s protect the heart should be made about specific molecules with specific evidence, not about the initials.
Frequently Asked Questions
References
- 1.Hernandez AF, Green JB, Janmohamed S, D'Agostino RB Sr, Granger CB, Jones NP, Leiter LA, Rosenberg AE, Sigmon KN, Somerville MC, Thorpe KM, McMurray JJV, Del Prato S; Harmony Outcomes committees and investigators. Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial. Lancet. 2018. PMID: 30291013.
- 2.GlaxoSmithKline. Effect of Albiglutide, When Added to Standard Blood Glucose Lowering Therapies, on Major Cardiovascular Events in Subjects With Type 2 Diabetes Mellitus (HARMONY OUTCOMES) — Study Results. ClinicalTrials.gov, NCT02465515. 2019. https://clinicaltrials.gov/study/NCT02465515
- 3.U.S. Food and Drug Administration. Drugs@FDA: Tanzeum (albiglutide) for injection — BLA 125431, status discontinued. FDA Drugs@FDA database. 2018. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=125431
- 4.Marso SP, Daniels GH, Brown-Frandsen K, et al.; LEADER Steering Committee; LEADER Trial Investigators. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 2016. PMID: 27295427.
- 5.Marso SP, Bain SC, Consoli A, et al.; SUSTAIN-6 Investigators. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med. 2016. PMID: 27633186.
- 6.Gerstein HC, Colhoun HM, Dagenais GR, et al.; REWIND Investigators. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Lancet. 2019. PMID: 31189511.
- 7.Gerstein HC, Sattar N, Rosenstock J, et al.; AMPLITUDE-O Trial Investigators. Cardiovascular and Renal Outcomes with Efpeglenatide in Type 2 Diabetes. N Engl J Med. 2021. PMID: 34215025.