Type 2 diabetics benefit from dulaglutide in several ways

The ADA/EASD guidelines recommend individualized therapy choices for type 2 diabetics. GLP-1 receptor agonists not only improve glycemic control, but also support weight loss, reduce the risk of cardiovascular disease, and preserve renal function. Dulaglutide has demonstrated clinically relevant additional benefit in both manifest or subclinical cardiovascular disease and chronic kidney disease.

If baseline therapy in combination with metformin is not effective in achieving adequate glycemic control, intensification of therapy is required. This should be based on the existing risk for cardiovascular disease, renal dysfunction, hypoglycemia, or the need for weight loss [1]. GLP-1 receptor agonists (GLP-1-RA) mimic the natural glucagon-like peptide-1 and are among the incretin mimetics. They promote the release of insulin from the beta cells of the pancreas and reduce the secretion of glucagon. In addition, additional cardio- and nephroprotective benefits have been identified in scientific studies. The results for the GLP-1-RA dulaglutide are particularly positive.

Scores in the prevention of cardiovascular events

According to current ADA/EASD guidelines, dulaglutide meets the requirements regarding initial injection therapy in patients who do not achieve adequate glycemic control on baseline therapy plus metformin and who are at increased risk for cardiovascular disease or hypoglycemia or the need for weight loss [1,2]. In Switzerland, Trulicity® (dulaglutide) has been newly indicated since last year for the prevention of cardiovascular events in adult patients with type 2 diabetes and already manifest or subclinical cardiovascular disease. This recommendation is mainly based on the results of the placebo-controlled, double-blind, long-term phase III clinical trial REWIND (n=9901) [3,4]. This study evaluated the effect of dulaglutide 1.5 mg on cardiovascular events in a broad patient population at varying levels of cardiovascular risk. The observation period was 5.4 years. The primary study end point was the incidence of major cardiovascular events according to the MACE*-3 criteria, a composite end point of time to occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Dulaglutide once weekly resulted in a clinically relevant 1% reduction in relative risk compared to placebo (p=0.028). This effect was independent of age, sex, BMI, baseline HbA1c, and duration of diabetes or of whether clinically manifest cardiovascular disease or only risk factors for it were already present. Furthermore, a reduction in the incidence of stroke has also been demonstrated (box) .

Further study demonstrates additional nephroprotective benefit

In addition to its beneficial effects on cardiovascular health, dulaglutide has also recently been shown to be of additional benefit in patients with type 2 diabetes and moderate or severe chronic kidney disease in combination with a short-acting insulin [5]. This is based on data from the AWARD-7 study, which showed that dulaglutide in combination with insulin lispro significantly reduced the risk of non-severe, symptomatic, confirmed hypoglycemia or severe hypoglycemia in this patient group compared with the combination of insulin glargine and insulin lispro [6].

Easy handling corresponds to patient preferences

Adherence is a critical factor for successful therapy, and patient-friendly application plays an important role. The special molecular structure of dulaglutide is associated with a prolonged half-life, which is why an injection only once a week is sufficient. This meets the need of many patients for treatment that is as simple as possible and causes as little stress as possible. The ease of use of dulaglutide in a ready-to-use pen, which was developed in collaboration with patients, also contributes to this.

* MACE = Major Adverse Cardiac Event

Literature:

1. “G-BA decision: double additional benefit for dulaglutide,” www.diabetologie-online.de/a/injektionstherapie-neue-daten-zu-dulaglutid-2072124, (last accessed Feb. 11, 2021).
2. Buse JB, et al: 2019 Update to: Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2020; 43(2): 487-493.
3. Gerstein HC, et al: Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. The Lancet 2019; 394(10193): 121-130.
4. Swiss Pharmacopoeia: https://compendium.ch, (last accessed Feb. 11, 2021).
5. GBA: Joint Federal Committee. Resolution of the Federal Joint Committee on an amendment to the Medicinal Products Guideline (AM-RL): Annex XII – Resolutions on the benefit assessment of medicinal products with new active substances in accordance with Section 35a of the German Social Code, Book V – Dulaglutide 2020, www.g-ba.de, (last accessed Feb. 11, 2021).
6. Tuttle KR, et al: Dulaglutide versus insulin glargine in patients with type 2 diabetes and moderate-to-severe chronic kidney disease (AWARD-7): a multicentre, open-label, randomised trial. Lancet Diabetes Endocrinol 2018; 6(8): 605-617.
7. Stiefelhagen P: Individual prevention: preventing stroke in diabetes. Diabetes Update 2019, https://link.springer.com/content/pdf/10.1007/s11298-019-7318-0.pdf

HAUSARZT PRAXIS 2021; 16(2): 16