Overweight type 1 diabetics in whom insulin therapy alone is not sufficient for glycemic control may receive additional oral treatment with the SGLT2 inhibitor dapagliflozin or the dual SGLT1/SGLT2 inhibitor sotagliflozin in the EU starting at a BMI of 27 kg/m2. However, it is advised to keep an eye on the risk of ketoacidosis.
Insulin remains the mainstay of drug treatment for type 1 diabetics, but glycemic targets are not always achieved by insulin therapy alone [1]. At this year’s virtual EASD, Prof. Dr. Björn Eliasson from the University of Gothenburg (Sweden) spoke about the current situation of complementary glucose-lowering pharmacotherapies in type 1 diabetes [2].
Dapagliflozin and sotagliflozin approved in the EU
Results from the DEPICT clinical trial program have shown that the SGLT2 inhibitor dapagliflozin as an add-on supports the achievement of glycemic goals in type 1 diabetic patients [1,2,7]. This positive study record led to the approval of dapagliflozin in the EU for patients with type 1 diabetes whose glucose levels cannot be adequately controlled with insulin treatment alone. According to a review article published in the journal Diabetes Therapy this year, patients who benefit from dapagliflozin supplementation include overweight patients with stable optimized insulin therapy and a low risk of ketoacidosis who have demonstrated good adherence. Dapagliflozin should not be prescribed in patients with low insulin requirements and a high risk of ketoacidosis, or if adherence to insulin treatment is difficult. In any case, adequate patient information is important.
In addition, sotagliflozin (Zynquista®) has been approved in the EU to improve glycemic control in addition to insulin therapy in adults with type 1 diabetes and a body mass index ≥27 kg/m2 who do not achieve adequate glycemic control despite optimal insulin therapy [3]. Sotagliflozin is an oral dual inhibitor of the type 1 and type 2 sodium-dependent glucose co-transporters (SGLT1 and SGLT2). SGLT1 provides glucose uptake in the gastrointestinal tract and SGLT2 provides glucose reuptake in the kidneys. In the pivotal phase III Tandem 3 study, 28.6% of type 1 diabetic patients dosed with sotagliflozin 400 mg once daily achieved HbA1c <7% (primary endpoint). In the placebo group, the figure was only 15.2%. However, it was found that significantly more ketoacidoses occurred in the sotagliflozin condition compared with placebo (3% vs. 0.6%) [4].
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Wang et al. investigated in a meta-analysis the efficacy of treatment with GLP-1-RAs as additive therapy for type 1 diabetics with regard to effects on the target parameters glycemic control, weight loss and insulin dosage. The conclusion of the study is that combined use of insulin and GLP-1 RAs is useful for patients with type 1 diabetes. Analysis of data from a total of 1093 studies showed that GLP-1 agonists and insulin combined resulted in significantly greater reductions in HbA1c levels and weight loss. Although the daily insulin dose did not decrease significantly, |
Pramlintide is on the market in the USA
Several years ago, the FDA approved the synthetic amylin analogue pramlintide for use in parallel with bolus insulin [5]. Amylin is a peptide hormone involved in the regulation of blood glucose levels after food intake. Synthesis takes place in the β-cells of the pancreas; amylin is stored and secreted together with insulin. Due to pancreatic dysfunction, patients with type 1 diabetes have decreased amyline concentrations. Amylin analogs simulate the mechanism of amylin, and pramlintide is currently the only available synthetic active ingredient. It stops the secretion of the hormone glucagon, thereby helping to lower blood sugar. In addition, the digestion process in the stomach is slowed down and the feeling of satiety lasts longer. Pramlintide is administered as an injection and used in combination with mealtime insulin.
Source: EASD 2020
Literature:
- Evans M, et al: Optimising the Benefits of SGLT2 Inhibitors for Type 1 Diabetes. Diabetes Therapy 2020; 11: 37-52.
- Eliasson B: Adjunctive therapies in people with type 1 diabetes – beyond insulin. What is he future of type 1 diabetes treatment? Prof. Dr. Björn Eliasson, EASD Virtual Meeting, 23.09.2020
- MMW: Dual SGLT inhibitor receives marketing approval. MMW – Advances in Medicine 161, 58 (2019). https://link.springer.com/article/10.1007%2Fs15006-019-0564-y
- Garg SK, et al: Effects of sotagliflozin added to insulin in patients with type 1 diabetes. N Engl J Med 2017; 377: 2337-2348.
- Ryan G, Briscoe TA, Jobe L: Review of pramlintide as adjunctive therapy in treatment of type 1 and type 2 diabetes. Drug Des Devel Ther 2009; 2: 203-214.
- Wang W, et al: Effects of insulin plus glucagon-like peptide-1 receptor agonists (GLP-1-RAs) in treating type 1 diabetes mellitus : a systematic review and meta-analysis. Diabetes Ther 2017; 8: 727-738
- Mathieu C, et al: Efficacy and Safety of Dapagliflozin in Patients With Inadequately Controlled Type 1 Diabetes (the DEPICT-2 Study): 24-Week Results From a Randomized Controlled Trial. Diabetes Care 2018; 41(9): 1938-1946.
HAUSARZT PRAXIS 2020; 15(11): 20 (published 11/18/20, ahead of print).
