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Tirzepatide, New Injectable Drug, Beats Insulin for A1C Reduction in Type 2

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Tirzepatide, New Injectable Drug, Beats Insulin for A1C Reduction in Type 2

A new investigational drug called tirzepatide was found to be superior to Tresiba (insulin degludec) — a long-acting insulin that is typically injected once daily — for long-term blood glucose control in people with type 2 diabetes, according to a new study published in the journal The Lancet.

Long-acting, or basal, insulin is typically prescribed as an additional treatment for type 2 diabetes when blood glucose levels aren’t adequately controlled by taking other diabetes drugs, such as metformin. While insulin is effective at lowering blood glucose levels, it comes with certain risks and side effects — the most severe risk being hypoglycemia (low blood glucose), which can be a medical emergency that leads to coma and even death. Taking insulin may also lead to weight gain in some people.

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For the latest study, the new drug under investigation — tirzepatide — belongs to the drug classes of GIP and GLP-1 receptor agonists. These types of drugs work by mimicking natural hormones that have a number of different glucose-lowering effects, including stimulating the release of insulin and slowing the absorption of glucose onto the bloodstream. Other GLP-1 receptor agonists include Byetta and Bydureon (exenatide), Trulicity (dulaglutide), and Victoza (liraglutide). Like basal insulin, these long-acting drugs are injected and are typically prescribed when oral drugs are inadequate for blood glucose control. There are currently no stand-alone GIP receptor agonists on the market.

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For the study of tirzepatide, 1,437 participants with type 2 diabetes at 122 locations in 13 countries were randomly assigned to one of four study groups. Three of the groups received a once-weekly injection of tirzepatide, containing 5, 10, or 15 milligrams of the drug. The fourth group received a once-daily injection of basal insulin, dosed according to their needs. Participants who received tirzepatide started out with a dose of 2.5 milligrams each week, which was increased by 2.5 milligrams every four weeks until the assigned dose was reached. Participants who received basal insulin started out receiving 10 units per day, and their dose was adjusted each week with the goal of achieving a fasting blood glucose level below 90 mg/dl. All groups followed their assigned treatment for a total of 52 weeks.

Tirzepatide reduces A1C substantially compared to basal insulin

The main endpoint the researchers were interested in was whether tirzepatide was superior to basal insulin at lowering A1C (a measure of long-term blood glucose control). For all of the study groups, the average A1C level at the beginning of the study was 8.17% — compared with the widespread recommendation that people with diabetes aim for an A1C level below 7.0%. After 52 weeks of treatment, the average A1C reduction in each of the study groups was 1.34% for basal insulin, 1.93% for 5 milligrams of tirzepatide, 2.20% for 10 milligrams of tirzepatide, and 2.37% for 15 milligrams of tirzepatide — demonstrating that the highest dose of tirzepatide reduced A1C by more than 1% compared with basal insulin, a dramatic difference.

What’s more, the proportion of people who achieved an A1C level below 7.0% was greater in all three tirzepatide groups (ranging from 82% to 93% of participants) than in the basal insulin group (61% of participants). The tirzepatide groups also experienced an average drop in body weight ranging from 7.5 to 12.9 kilograms (16.5 to 28.4 pounds) for the three different doses, while the basal insulin group saw an average weight gain of 2.3 kilograms (5.1 pounds). At the beginning of the study, the average body weight in each of the study groups was 94.3 kilograms (207.9 pounds).

The most commonly reported adverse events in the groups that took tirzepatide were gastrointestinal problems like nausea, diarrhea, reduced appetite, and vomiting, which tended to decrease over time. Severe hypoglycemia — less than 54 mg/dl — was reported in 1% to 2% of each of the tirzepatide groups, compared with 7% of the basal insulin group.

The researchers concluded that based on the study results, tirzepatide was found to be a superior treatment for type 2 diabetes than basal insulin, and carried a safety profile similar to that of GLP-1 receptor agonists currently on the market. No announcement has yet been made about whether, or when, tirzepatide is expected to be available commercially as a treatment for type 2 diabetes after gaining regulatory approval.

Want to learn more about this treatment? Read “Tirzepatide: New Diabetes Treatment Shows Promising Results.”

Quinn Phillips

Quinn Phillips

Quinn Phillips on social media

A freelance health writer and editor based in Wisconsin, Phillips has a degree from Harvard University. He is a former Editorial Assistant for Diabetes Self-Management and has years of experience covering diabetes and related health conditions. Phillips writes on a variety of topics, but is especially interested in the intersection of health and public policy.

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