Semaglutide 2.4 mg in obesity-related HFpEF with type 2 diabetes: phase 3 registry results

The study

This report is based on the results entry for registry record NCT04916470 on ClinicalTrials.gov. The sponsor is Novo Nordisk A/S. The record lists the study as phase 3, with enrolment of 617 participants.

Participants had obesity-related heart failure with preserved ejection fraction (HFpEF) and type 2 diabetes. They were assigned by chance to semaglutide 2.4 mg or to a "dummy" (placebo) medicine. Both were given as one injection a week. Participants also had talks with study staff about a healthy lifestyle and physical activity.

The study lasted about 59 weeks, with 12 clinic visits. These included questionnaires, 6-minute walking tests, heart tests and blood tests. The record has two primary outcomes, both measured from baseline to week 52: change in the KCCQ (Kansas City Cardiomyopathy Questionnaire) Clinical Summary Score, and percentage change in body weight.

What they found

KCCQ Clinical Summary Score. The mean score rose by 14.4 with semaglutide 2.4 mg and by 7.6 with placebo. The record gives the treatment difference as 7.3 (ANCOVA, p <0.0001).

Body weight. Mean body weight fell in both groups. The mean percentage change was -10.2 with semaglutide and -3.2 with placebo. The record gives the treatment difference as -6.4 (ANCOVA, p <0.0001).

The record also lists a "spread" for each group (18.3 and 18.8 for the KCCQ score, 6.8 and 5.9 for weight). It does not say which measure of spread this is. It does not report confidence intervals in this extract.

How much weight to give it

This is a registry results entry, not a peer-reviewed paper. Participants were assigned by chance to semaglutide or a "dummy" medicine in a phase 3 study. The record lists enrolment of 617 participants. It does not report a power calculation.

There are clear limits.

• The KCCQ score is reported by patients. The extract does not say whether participants and staff were blinded, so the risk of bias cannot be judged.
• Both primary outcomes are symptom, function and weight measures. The extract reports no heart failure hospitalisations, deaths or other hard outcomes.
• The extract does not report safety or side effects, how many people stopped treatment, or how missing data were handled.
• The record does not explain what a higher KCCQ score means or what size of change matters to patients. Check this in the full paper.
• Sponsor-run trials need careful reading of the full methods and the full set of results.

The record states no authors' conclusion, so there is no author view to compare with.

For your clinic

The results suggest that, in people with obesity-related HFpEF and type 2 diabetes, the KCCQ Clinical Summary Score increased more with semaglutide 2.4 mg than with placebo over 52 weeks (treatment difference 7.3, p <0.0001), and weight fell more. This is a general finding for the trial group. It is not advice for any one patient.

Before changing practice, read the full peer-reviewed paper. Look for safety data, the effect on hospitalisation and death, and how many patients had real improvement in symptoms. Also check how closely the trial participants resemble your patients. Cost and the available product and indication also matter in India (see the India box).