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10-14-2020 | Tirzepatide | At a glance | Article

A quick guide to the SURPASS and SURMOUNT trials

Phase 3 trials of tirzepatide in type 2 diabetes and obesity

Author:
Eleanor McDermid

medwireNews: Tirzepatide (formerly known as LY3298176) is a novel glucose-lowering medication that stimulates the receptors for both glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide (GLP)-1.

Phase 2 findings published in The Lancet in 2018 were promising, with the medication showing dose-dependent effects on glucose levels and bodyweight. It outperformed dulaglutide 1.5 mg/day at the highest doses, albeit in a small group of study participants.

The phase 3 trials, the most advanced of which are scheduled to complete in late 2020, are testing the medication as monotherapy, as an add-on to other treatments, and against established glucose-lowering drugs in people with type 2 diabetes, as well as a weight-loss agent in people with diabetes and obesity.

All the trials are sponsored by tirzepatide’s manufacturer, Eli Lilly. We provide a round-up of them below and will update this page with the results as they are released.

And click here for a linked commentary, in which Medicine Matters editorial board member John Wilding outlines the potential advantages of dual GIP-GLP-1 agonists as a treatment approach for people with type 2 diabetes.

The SURPASS trials

SURPASS-1

Trial population: Drug-naïve people with type 2 diabetes

Comparator treatment: Placebo

NCT03954834; estimated study completion in November 2020

This trial is testing tirzepatide at doses of 5, 10, and 15 mg, administered as a weekly subcutaneous injection, in people with type 2 diabetes who have elevated glycated hemoglobin (HbA1c) levels despite diet and exercise interventions.

The primary outcome is change in HbA1c between baseline and 40 weeks of treatment.

SURPASS-2

Trial population: People taking metformin monotherapy

Comparator treatment: Semaglutide

NCT03987919; estimated study completion in February 2021

In SURPASS-2, tirzepatide at the same three weekly doses (5, 10, and 15 mg) is up against weekly injections of the GLP-1 receptor agonist semaglutide.

Both will be given as an add-on to metformin for 40 weeks in people taking no other glucose-lowering medications.

SURPASS-3

Trial population: People taking metformin with/without an SGLT2 inhibitor

Comparator treatment: Insulin degludec

NCT03882970; estimated study completion in January 2021

In this trial, the investigators are comparing the efficacy of weekly tirzepatide (5, 10, and 15 mg) with daily insulin degludec in people who have poorly controlled blood glucose despite stable treatment with metformin with or without an SGLT (sodium-glucose cotransporter)2 inhibitor.

This trial will run for 52 weeks, with the primary endpoint again being change in HbA1c.

SURPASS-4

Trial population: People taking metformin with/without an SGLT2 inhibitor

Comparator treatment: Insulin glargine

NCT03730662; estimated study completion in June 2021

This trial is identical in design to SURPASS-3, except the comparator long-acting insulin is glargine rather than degludec.

SURPASS-5

Trial population: People taking insulin glargine

Comparator treatment: Placebo

NCT04039503; estimated study completion in February 2021

The SURPASS-5 trial is testing tirzepatide in people with insulin-dependent type 2 diabetes who have uncontrolled blood glucose despite treatment with insulin glargine, with or without metformin.

The usual three doses (5, 10, and 15 mg) are being given as an add-on to glargine and the effects on HbA1c compared against placebo over 40 weeks.

SURPASS-AP-Combo

Trial population: People taking metformin with/without a sulfonylurea

Comparator treatment: Insulin glargine

NCT04093752; estimated study completion in March 2022

This trial is testing tirzepatide versus insulin glargine, over a 40-week period, in people taking metformin with or without a sulfonylurea of at least half the maximum dose.

SURPASS-CVOT

Trial population: People with type 2 diabetes, confirmed atherosclerotic cardiovascular disease, and overweight

Comparator treatment: Dulaglutide

NCT04255433; estimated study completion in October 2024

For its cardiovascular outcomes trial, tirzepatide is up against dulaglutide 1.5 mg, which has a confirmed cardioprotective effect.

The investigators are assessing a three-point major adverse cardiovascular event endpoint (myocardial infarction, stroke, and cardiovascular death), over an estimated maximum of 54 months.

Trials for the Japanese market

SURPASS J-mono

Trial population: People who are drug-naïve or taking monotherapy (discontinued before baseline)

Comparator treatment: Dulaglutide

NCT03861052; estimated study completion in April 2021

This trial in Japanese people with type 2 diabetes is comparing weekly tirzepatide (5, 10, or 15 mg) against weekly dulaglutide 0.75 mg in people taking no other glucose-lowering medications during the trial.

Follow-up will last for 52 weeks and the primary endpoint is change in HbA1c.

SURPASS J-combo

Trial population: People taking antidiabetes medications other than incretin-based classes

Comparator treatment: None

NCT03861039; estimated study completion in March 2021

This safety study will monitor adverse events in Japanese people given tirzepatide (5, 10, or 15 mg) in addition to non-incretin-based antidiabetes medications over 52 weeks of treatment.

A trial of tirzepatide for obesity

SURMOUNT-1

Trial population: People with type 2 diabetes plus obesity or BMI 27 kg/m2 and related comorbidities

Comparator treatment: Placebo

NCT04184622; estimated study completion in May 2024

The SURMOUNT-1 trial is testing the ability of tirzepatide to produce weight loss in people with diabetes and obesity.

Participants will take tirzepatide at doses of 5, 10, or 15 mg, and the co-primary endpoints are the percent change in bodyweight and the proportion of people attaining at least a 5% reduction in their baseline bodyweight by week 72.

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2020 Springer Healthcare Ltd, part of the Springer Nature Group

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