Effectiveness and safety of tirzepatide compared to insulin degludec in patients with type 2 diabetes.

In a nutshell

This study compared the effectiveness and safety of tirzepatide to insulin degludec (Tresiba) in patients with uncontrolled type 2 diabetes (T2D). The data showed that tirzepatide produced better blood glucose control and body weight improvements with reduced risk of hypoglycemia, compared to degludec in these patients.

Some background

Tirzepatide is a new, weekly administered T2D treatment given by injection under the skin. It is both a glucose-dependent insulinotropic polypeptide (GIP) and a glucagon-like peptide-1 receptor agonist (GLP-1 RA). Tirzepatide works by increasing natural insulin secretion based on blood glucose levels and prevents increases in blood glucose.

Insulin degludec is an ultra-long acting, daily injected basal insulin that controls blood glucose. The recommended treatment in patients with T2D uncontrolled by standard therapies such as metformin (Glucophage) or sodium-glucose cotransporter-2 inhibitors (SGLT2i) is basal insulin or GLP-1 RAs. However, dangerously low blood glucose (hypoglycemia) is a concern. The effects of tirzepatide on blood glucose control, body weight, and safety compared with insulin degludec remain unclear.

Methods & findings

This study included 1437 patients with uncontrolled T2D. 358 patients were given 5 mg of tirzepatide (group 1), while 360 patients received 10 mg of tirzepatide (group 2), and 359 patients received 15 mg of tirzepatide (group 3). Tirzepatide was given once weekly by injection. 360 patients were given once-daily insulin degludec (group 4) by injection until a fasting blood glucose of less than 90 mg/dl was achieved. Treatments were given for 52 weeks. Changes in HbA1c (a measure of blood glucose control over the past 2-3 months) and body weight were evaluated. 

At week 52, an average HbA1c reduction of 1.93% was seen in group 1, a reduction of 2.2% in group 2, 2.37% in group 3, and of 1.34% in group 4. The proportion of patients in groups 1-3 that achieved an HbA1c level below 7% was significantly higher (82%-93%) compared to 61% for insulin degludec.

In groups 1-3 there was a significant weight reduction of 7.5 kg to 12.9 kg compared to a 2.3 kg increase in bodyweight in group 4.

The most common side effects reported in groups 1-3 were digestive problems such as nausea (12.24%), diarrhea (15-17%), decreased appetite (6-12%), and vomiting (6-10%). Patients treated with tirzepatide had less hypoglycemia (1-2%) than those given insulin degludec (7%). 

The bottom line

The study showed that tirzepatide resulted in greater blood glucose control and body weight reductions and lower hypoglycemia risk compared to insulin degludec in patients with T2D.

The fine print

Patients and investigators were aware of treatments given and this could have influenced the self-reporting of gastrointestinal side effects. This study was funded by Eli Lilly and Company, the manufacturer of tirzepatide

Published By :

Lancet (London, England)

Date :

Aug 06, 2021

Original Title :

Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or without SGLT2 inhibitors in patients with type 2 diabetes (SURPASS-3): a randomised, open-label, parallel-group, phase 3 trial.

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