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HomeA FocusSTEP 2 trial: Semaglutide hope for patients with type 2 diabetes

STEP 2 trial: Semaglutide hope for patients with type 2 diabetes

Type 2 diabetes patients treated with the new drug Semaglutide achieved an average weight loss of nearly 10kg and a significant improvement in blood glucose control, according to the STEP 2 multi-centre trial. Last month, STEP 1 reported that more than a third of adults who took Semaglutide lost more than 20% (15kg) of their body weight.

Semaglutide, already approved and used for treatment of diabetes, has been submitted for regulatory approval in the USEU and UK.

STEP 1 found that in addition to weight loss, Semaglutide also improved cardiovascular risk factors including greater reductions in waist circumference, BMI, systolic and diastolic blood pressures, HbA1c, fasting plasma glucose, C-reactive protein, and fasting lipid levels, as well as physical functioning scores and quality of life.

STEP 2, led by Melanie Davies, professor of diabetes medicine at the University of Leicester and the co-director of the Leicester Diabetes Centre, showed that two thirds of patients with type 2 diabetes that were treated with weekly injections of a 2.4mg dose of Semaglutide were able to lose at least 5% of their body weight and achieved significant improvement in blood glucose control.

More than a quarter of patients were able to lose more than 15% of their body weight – far above that which has been observed with any other medicine administered to people with diabetes.

Davies said: “These results are exciting and represent a new era in weight management in people with type 2 diabetes – they mark a real paradigm shift in our ability to treat obesity, the results bring us closer to what we see with more invasive surgery.

“It is also really encouraging that along with the weight loss we saw real improvements in general health, with significant improvement in physical functioning scores, blood pressure and blood glucose control”.

The STEP 2 global multi-centre trial was conducted at 149 sites in 12 countries across North America, Europe, South America, the Middle East, South Africa and Asia, involving 1,210 patients with type 2 diabetes whose current treatment was not achieving sufficient blood sugar control, for instance through diet and exercise, or through the use of metformin and other glucose lowering medicines used to control the disease.

It is one of a portfolio of studies conducted as part of the Semaglutide Treatment Effect for people with obesity Programme (STEP) programme.

Davies has been involved in all four of the STEP clinical trials involving Semaglutide for weight management completed so far, where the medication was shown to help patients achieve an average weight of loss of between 10kg and 17kg of body weight.

Being overweight or obese is a significant contributor to type 2 diabetes. Many patients can manage their type 2 diabetes by eating a healthy diet, taking regular exercise, and using medications to help control blood sugar, or achieve glycaemic control but for a significant minority of patients who have not seen much improvement in spite of these methods, Semaglutide is a promising development.

Rachel Batterham, professor of obesity, diabetes and endocrinology who leads the Centre for Obesity Research at University College London (UCL) and the UCLH Centre for Weight Management, is one of the principal authors on STEP 1, which involved almost 2,000 people in 16 countries. “The impact of obesity on health has been brought into sharp focus by COVID-19 where obesity markedly increases the risk of dying from the virus, as well as increasing the risk of many life-limiting serious diseases including heart disease, type 2 diabetes, liver disease and certain types of cancers. This drug could have major implications for UK health policy for years to come.”

 

Study details
Semaglutide 2·4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2): a randomised, double-blind, double-dummy, placebo-controlled, phase 3 trial

Melanie Davies, Louise Færch, Ole K Jeppesen, Arash Pakseresht, Sue D Pedersen, Leigh Perreault, Julio Rosenstock, Iichiro Shimomura, Adie Viljoen, Thomas A Wadden, Ildiko Lingvay, STEP 2 Study Group

Published in The Lancet on 2 March 2021

Abstract
Background
This trial assessed the efficacy and safety of the GLP-1 analogue once a week subcutaneous semaglutide 2·4 mg versus semaglutide 1·0 mg (the dose approved for diabetes treatment) and placebo for weight management in adults with overweight or obesity, and type 2 diabetes.
Methods
This double-blind, double-dummy, phase 3, superiority study enrolled adults with a body-mass index of at least 27 kg/m 2 and glycated haemoglobin 7–10% (53–86 mmol/mol) who had been diagnosed with type 2 diabetes at least 180 days before screening. Patients were recruited from 149 outpatient clinics in 12 countries across Europe, North America, South America, the Middle East, South Africa, and Asia. Patients were randomly allocated (1:1:1) via an interactive web-response system and stratified by background glucose-lowering medication and glycated haemoglobin, to subcutaneous injection of semaglutide 2·4 mg, or semaglutide 1·0 mg, or visually matching placebo, once a week for 68 weeks, plus a lifestyle intervention. Patients, investigators, and those assessing outcomes were masked to group assignment. Coprimary endpoints were percentage change in bodyweight and achievement of weight reduction of at least 5% at 68 weeks for semaglutide 2·4 mg versus placebo, assessed by intention to treat. Safety was assessed in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT03552757 and is closed to new participants.
Findings
From June 4 to Nov 14, 2018, 1595 patients were screened, of whom 1210 were randomly assigned to semaglutide 2·4 mg (n=404), semaglutide 1·0 mg (n=403), or placebo (n=403) and included in the intention-to-treat analysis. Estimated change in mean bodyweight from baseline to week 68 was −9·6% (SE 0·4) with semaglutide 2·4 mg vs −3·4% (0·4) with placebo. Estimated treatment difference for semaglutide 2·4 mg versus placebo was −6·2 percentage points (95% CI −7·3 to −5·2; p<0·0001). At week 68, more patients on semaglutide 2·4 mg than on placebo achieved weight reductions of at least 5% (267 [68·8%] of 388 vs 107 [28·5%] of 376; odds ratio 4·88, 95% CI 3·58 to 6·64; p<0·0001). Adverse events were more frequent with semaglutide 2·4 mg (in 353 [87·6%] of 403 patients) and 1·0 mg (329 [81·8%] of 402) than with placebo (309 [76·9%] of 402). Gastrointestinal adverse events, which were mostly mild to moderate, were reported in 256 (63·5%) of 403 patients with semaglutide 2·4 mg, 231 (57·5%) of 402 with semaglutide 1·0 mg, and 138 (34·3%) of 402 with placebo.
Interpretation
In adults with overweight or obesity, and type 2 diabetes, semaglutide 2·4 mg once a week achieved a superior and clinically meaningful decrease in bodyweight compared with placebo.
Funding
Novo Nordisk.

 

[link url="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00213-0/fulltext"]The Lancet study (Restricted access)[/link]

 

[link url="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)00377-9/fulltext"]The Lancet comment (Restricted access)[/link]

 

See also from the MedicalBrief archives:

 

[link url="https://www.medicalbrief.co.za/archives/regulatory-approval-sought-for-gamechanger-obesity-drug/"]STEP 1: Regulatory approval sought for ‘gamechanger’ obesity drug[/link]

 

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