Semaglutide can reduce the risk of developing type 2 diabetes for overweight or obese people by a notable 60%, underscoring the tight link between obesity and type 2 diabetes, according to a recent 68-week study modelling future outcomes.
The polypeptide semaglutide is prescribed by physicians to treat type 2 diabetes: the US Federal Drug Administration (FDA) recently approved the use of Novo Nordisk’s Ozempic and Rybelsus as a once-weekly injection or as a tablet, respectively. A once-weekly injection of semaglutide with the brand name Wegovy has more recently been approved as a weight loss treatment.
In this latest study, researchers showed that the weekly dose of 2.4mg of semaglutide lowered the 10-year risk of developing type 2 diabetes by a significant 60%, from 18.2% to 7.1%. Although people with prediabetes were at greater risk initially, semaglutide reduced their risk by a similar amount to those with healthy blood sugar levels.
The research was presented last week at the annual meeting of the European Association for the Study of Diabetes in Stockholm, Sweden.
Body weight and the diabetes risk increased for participants who were switched to a placebo after 20 weeks, suggesting that sustaining a reduction in diabetes risk requires continued semaglutide treatment.
Cardiometabolic disease staging (CMDS), which the researchers describe as a “validated staging tool” to assess the 10-year risk of type 2 diabetes, modelled participants’ future health outcomes. The tool can also predict the risk of cardiovascular disease.
Fighting diabetes by fighting obesity
Study author Dr Timothy Garvey, senior scientist at the University of Alabama at Birmingham Nutrition Obesity Research Centre, told Medical News Today: “I’ve been making the case for some time that weight loss should be a primary therapeutic modality in type 2 diabetes as a first-line therapy, not only to control the haemoglobin A1C, and the blood sugars, but to prevent and treat all other complications suffered by overweight or obese patients.
“These patients have high rates of obstructive sleep apnea, and obesity also worsens the dyslipidemia, hypertension, (and) the glucose control; increases cardiovascular risk factors, increases the fat content in the liver and non-alcoholic fatty liver disease.
“So weight loss will tackle all of those issues, whereas diabetes medicines alone… many won’t get that job done.”
Dr Samuel Klein, professor of cell biology and physiology at the Washington University School of Medicine in St. Louis, who was not involved in the research, agreed with Garvey.
He told MNT that “(t)he real primary treatment for type 2 diabetes is really to reduce body weight in people who (have obesity). This analysis suggested that’s the case… if you reduce body weight with newer medications you can reduce the risk of developing type 2 diabetes”.
How semaglutide works
“Semaglutide is a GLP-1 receptor agonist and increases insulin secretion in response to a rise in glucose,” said Garvey. “But at the higher dose range, it also enters the brain and acts on satiety centres, suppressing appetite to cause weight loss.”
In terms of safety, he said: “When you’re escalating the dosage, you start low and build up to mainly mitigate the nausea and gastrointestinal symptoms: nausea, vomiting, diarrhoea. That occurs in about 40% of patients. It’s usually self-limited, improves over time, and you can continue the medicine.”
He noted, however, that semaglutide can increase the chance of gall bladder disease, so it should not be prescribed for a person “with active gall bladder disease symptoms passing gallstones, having cholecystitis, or any kind of gallbladder problem”.
A possible connection to pancreatitis, he suggested, might be an additional product of gall bladder issues.
Garvey added that the medication cannot be used by people with nodular thyroid cancer, because of what has been observed in rats.
Klein agreed, but added: “We don’t have long-term data, and that would need to be monitored carefully. But I don’t think you should wait for those data to come back to prevent prescribing it because it would be a decade before you can get all of that data.”
Who should take semaglutide?
While the value of semaglutide for a patient is a judgment call only their physician can make, Klein suggested: “If you want to reduce the risk of diabetes, it should be limited to those with prediabetes because they are at high risk.”
He described such people as having “evidence of abnormal blood lipids, blood pressure, abnormal glucose tolerance tests, for example, or a high fasting glucose”.
He made the case for prescribing semaglutide to individuals who are obese but show no signs of being at risk for diabetes. “I speak about the complications (of obesity) in two ways. One is cardiometabolic, the other is biomechanical. Complications are due to carrying around a heavy body mass over a longer period of time, like sleep apnea, like osteoarthritis, gastroesophageal reflux, urinary incontinence, immobility, issues that deal with quality of life,” he said.
Weighing the cost and benefits
Semaglutide’s pricing may be an issue for some patients, and it is not clear how medical insurance companies will embrace funding its use.
The latest data from the National Health and Nutrition Examination Survey (NHANES) for the years 2017–2018 show that 42.4% of Americans have obesity, and this percentage surpasses 70% if it includes overweight people.
The obesity bias
Garvey said a reluctance to pay for obesity treatment “reflects a bias against obesity”. “Many healthcare professionals .. think obesity is a lifestyle choice, not a disease.”
Klein said it was becoming more “abnormal” to see lean North Americans, and “normal to be overweight and obese”. He added that the buck “stops with the person eating the food, but it’s difficult to do that”.
“This is due to this interaction between our genes driving us to like food, want food, eat food, as well as want to not become a very low body weight to die from starvation, all mixed together with our environment.”
Study details
Semaglutide 2.4 mg reduces the 10-year type 2 diabetes risk in people with overweight or obesity
W. Timothy Garvey, Lua Wilkinson, Peter Laursen, Anders Rinnov, Thomas Holst-Hansen.
Presented at the 58th EASD Annual Meeting on 21 September 2022
Background and aims
The effect of once-weekly s.c. semaglutide 2.4 mg on the risk of developing type 2 diabetes (T2D) in people with obesity is unknown. Using data from the Semaglutide Treatment Effect in People with obesity (STEP) programme (STEP 1 and STEP 4) we assessed the risk of developing T2D over 10 years.
Materials and methods
Weight management with semaglutide 2.4 mg vs placebo plus diet and exercise was assessed in participants with overweight or obesity in STEP 1 (68 weeks) and STEP 4 (20-week run-in on semaglutide 2.4 mg, 48-week randomised withdrawal). To determine the percentage chance of an individual developing T2D in the next 10 years, the 10-year T2D risk was calculated post-hoc using Cardiometabolic Disease Staging (CMDS), which is a validated staging tool that uses Bayesian logistic regression of T2D risk factors including age, sex, race, BMI, triglycerides, HDL, blood pressure, and blood glucose, to predict an individual's percentage risk of developing T2D in the next 10 years.
Results
In STEP 1 the 10-year risk scores of developing T2D after 68 weeks of treatment decreased from 18.2% to 7.1% with semaglutide 2.4 mg, and 17.8% to 15.6% with placebo (61% vs 13% reduction [p<0.01]. In STEP 4 most of the risk score reduction with semaglutide 2.4mg occurred during weeks 0-20, from 20.6% to 11.4%; risk score decreased further to 7.7% with continued semaglutide 2.4 mg during weeks 20-68 but increased to 15.4% with switch to placebo (32% reduction vs 41% increase [p<0.01]. In STEP 1, week 0 risk scores were higher in participants with prediabetes vs normoglycaemia, but treatment effects were comparable at week 68 (p=0.45 for interaction in both groups). In STEP 1, risk score changes mirrored weight loss which was 17% with 2.4mg vs 3% with placebo. In STEP 4, weight loss was 11% for weeks 0-20 with semaglutide 2.4mg and a further 9% with continued semaglutide 2.4 mg vs a 6% regain with switch to placebo for weeks 20-68.
Conclusion
In summary, treatment with semaglutide 2.4 mg reduces the 10-year risk of T2D by ~60% regardless of initial glycaemic status, with sustained treatment required to maintain this benefit. These data suggest semaglutide 2.4 mg could help prevent T2D in people with obesity.
EASD presentation (Open access)
See more from MedicalBrief archives:
Maintenance semaglutide injections led to continued weight loss — STEP 4
STEP 2 trial: Semaglutide hope for patients with type 2 diabetes
Diabetes drug helps obese patients shed weight – US study