Data shows switch towards semaglutide for treatment of type 2 diabetes

Over the past five years there has been a sharp trend towards the use of semaglutide in both oral and injectable form to treat people with type 2 diabetes, new research shows.

Presented at this year’s EASD meeting, the study is authored by Professor Elisabetta Patorn, Dr Alexander Kutz and colleagues from the Brigham and Women`s Hospital and Harvard University, Boston.

Currently, based on clinical experience, the authors estimate between 30 per cent and 40 per cent of all diabetes drugs prescribed in the USA belong to the incretin class.

Incretin-based diabetes drugs work by increasing the levels of incretin hormones in the blood, including glucagon-like-peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP).

This in turn inhibits glucagon release, which increases insulin secretion, decreases gastric emptying, and decreases blood glucose levels.

An additional effect of these drugs – and indeed why their use and profile are increasing globally – is increased satiety or fullness, leading to decreased calorie consumption and weight loss.

There are people without type 2 diabetes using these drugs for weight loss alone, which has caused shortages of the drugs in many countries.

In this study, the authors evaluated trends in use of incretin-based medications and assessed predictors of initiation of specific incretin-based agents.

Using a large U.S. health insurance database (Optum`s Clinformatics Data Mart), the authors conducted a retrospective cohort study including 1,065,592 adult patients with type 2 diabetes who were prevalent or incident users of incretin-based medications (oral [semaglutide], injectable GLP-1 receptor agonists (including lixisenatide, exenatide, liraglutide, dulaglutide or semaglutide), or dipeptidyl peptidase 4 inhibitors [DPP-4i], including sitagliptin, linagliptin, saxagliptin or alogliptin) between 2018 and the first quarter of 2022 (2022Q1). Quarterly trends in use of incretin-based medications were plotted.

While DPP-4i was the most frequently used incretin-based medication in 2018 Q1 (62.4 per cent among users of incretin-based medications with type 2 diabetes), its percentage decreased to 38.7 per cent in 2022 Q1.

During the same time, the percentage of injectable GLP-1RA users increased from 37.6 per cent to 56.6 per cent.

Users of oral semaglutide were first observed in 2019 Q4 and accounted for 4.7 per cent of incretin users in 2022 Q1.

Among users of GLP-1RA, there was a decrease in users of liraglutide (from 44.2 per cent in 2018Q1 to 10.0 per cent in 2022Q1) and exenatide (15 per cent to 3.8 per cent), but an increase in users of injectable semaglutide (0.0 per cent to 33.7 per cent), dulaglutide (35.2 to 42.1 per cent), and oral semaglutide (0.0 per cent [2019Q4] to 7.7 per cent).

When considering users of only oral incretin-based medications, sitagliptin was the most frequently used agent over the entire study time (decreasing from 62 per cent to 49.5 per cent).

While percentages for linagliptin and saxagliptin users decreased over time, oral semaglutide showed the largest increase (from 0.2 per cent in 2019Q4 to 23.1 per cent in 2022Q1).

When compared with initiators of DPP-4i, those initiating GLP-1RA were more likely to have obesity if using injectables (+64 per cent increase in relative risk), and more likely to have obesity if using orals (+54 per cent); and overall more likely to be seen by an endocrinologist (+18-46 per cent more likely oral/injectable respectively); but less likely to have prevalent CKD (14 per cent less likely for injectable and 19 per cent less likely for oral); and less likely to have dementia (34 per cent less likely for injectable, 49 per cent less likely for oral).

The authors conclude: “Among adults with type 2 diabetes, there was a switch in the likelihood of receiving DDP-4i (more frequently prescribed in earlier years) to GLP-1RA (more frequently prescribed in recent years).

“While the use of oral semaglutide increased in recent years, injectable GLP-1RA are still the preferred incretin-based treatment.”

While the authors acknowledge the surging demand for both injectable and more recently oral semaglutide around the world for weight loss, they highlight that for now it should be restricted to patients with both type 2 diabetes and overweight or obesity.

They explain: “It is likely that oral semaglutide will become one of the leading drugs among oral users of incretin-based medications, but sitagliptin (and other DPP-4i) may be still preferred in older and multimorbid patients at higher risk of frailty, for example in the setting of nursing homes.”

Regarding ongoing developments in this drug class, the authors say there is no doubt that tirzepatide, the new glucose-dependent insulinotropic polypeptide (GIP) drug currently going through regulatory approval for weight loss, will add value to the arsenal of drugs against hyperglycaemia, obesity, and related comorbidities in people with type 2 diabetes.

They say: “The effects of tirzepatide on glycaemia are similar or even superior to those achieved with insulin therapy, however, without concerns about hypoglycaemia and weight gain, also accompanied by a convenient once-weekly administration scheme.

“In a significant proportion of cases, tirzepatide-induced weight loss is comparable with the effects of metabolic surgery, setting the stage for future head-to-head trials between the two weight loss strategies.”

They add: “Nevertheless, we need more evidence before adopting widespread use of the tirzepatide in newly diagnosed type 2 diabetes, as unanswered questions remain about cost effectiveness, risk-benefit balance in lean people with type 2 diabetes and the elderly, and also cardiovascular benefits in the primary and secondary prevention setting.”