Dulaglutide versus Insulin Glargine for Type 2 Diabetes

Does a once-weekly dulaglutide provide similar efficacy compared to basal insulin for patients with type 2 diabetes?

In the pharmacological options available for type 2 diabetes, basal insulin such as insulin glargine is an effective method in control fasting blood sugar. However, the use of insulin is associated with hypoglycemia and weight gain, and good adherence to insulin therapy is crucial to achieving desired glycemic control. Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) are a novel drug class that showed efficacy in improving glycemic control and weight loss while associated with less frequent administration and lower incidences of hypoglycemia. Several studies have been conducted to compare dulaglutide, a GLP-1 RA, with insulin glargine. Therefore, Xu et al. conducted this meta-analysis to assess the efficacy and safety of two different doses of dulaglutide (1.5 mg and 0.75 mg) versus insulin glargine.

This systematic review selected all eligible studies from PubMed, Embase, and Cochrane Library from inception until December 2020 and included five studies that meet the inclusion criteria. Inclusion criteria were randomized controlled trials that assessed the efficacy and safety of dulaglutide with insulin glargine, patients with type 2 diabetes, minimum treatment duration of 12 weeks. All eligible studies were open-label and parallel-group trials with duration ranged from 34 to 78 weeks.

The efficacy outcomes assess the mean change from baseline in HbA1c levels and body weight. Dulaglutide dose of 1.5 significantly reduced the HbA1c levels by 0.33% (95% CI -0.52 to -0.15) compared to insulin glargine. However, the dulaglutide dose of 0.75 mg non-significantly reduced the HbA1c levels by 0.21% (95% CI -0.43 to 0.01). In the mean change from baseline body weight, 1.5 mg and 0.75 dulaglutide reduced the body weight by 3.15 kg (95% CI -3.84 to -2.47) and 2.23 kg (95% CI -2.85 to -1.61) compared to insulin glargine, respectively.

In the safety outcomes, insulin glargine was associated with more hypoglycemia episodes, while dulaglutide was associated with more gastrointestinal adverse events (nausea, diarrhea, and vomiting). Dulaglutide dose of 1.5 mg and 0.75 mg reduced the rate of total hypoglycemia by 3.80 (95% CI -6.55 to -1.05) and 3.91 (95% CI -6.63 to -1.19) compared to insulin glargine, respectively. A few incidences of increased lipase level more than three times the upper limit of normal reported associated with dulaglutide.

This study showed that dulaglutide 1.5 mg met the statistical criteria for superiority, and dulaglutide 0.75 mg met the criteria for non-inferiority in the efficacy outcomes compared with insulin glargine. The author concluded that the use of dulaglutide is associated with better glycemic control and weight management and a lower risk of hypoglycemia. Besides, dulaglutide is a long-acting agent that only requires once-weekly subcutaneous injection, may play a key role in assuring good adherence for many patients.  One limitation in this study is that due to the nature of a systematic review, the authors did not provide any comment regarding bolus insulin between the two groups, such as an increase or reduction in bolus insulin dosing and associated glycemic levels. On the other hand, this study did not include some other benefits of dulaglutide. For example, in the REWIND trial, dulaglutide provided benefits in cardiovascular protection with and without metformin and was showed to improve cognitive functions in patients with type 2 diabetes.

Practice Pearls:

• Dulaglutide 1.5 mg significantly reduced HbA1c compared to insulin glargine for patients with type 2 diabetes.
• Other benefits of dulaglutide include weight loss and a lower incidence of hypoglycemia.
• Dulaglutide is a potential therapy that is more suitable than basal insulin.

References:

Xu, Jun et al. “Efficacy and safety of dulaglutide compared with glargine in patients with type 2 diabetes: A systematic review and meta-analysis.” Journal of clinical pharmacy and therapeutics vol. 46,5 (2021): 1245-1253.

Cuckierman-Yaffe, et al. “Effect of dulaglutide on cognitive impairment in type 2 diabetes: an exploratory analysis of the REWIND trial” The Lancet, vol 19, issue 7, 2020, p 582-590.

Ding Nguyen, PharmD Candidate, University of South Florida Taneja College of Pharmacy