Metabolic Control in Type 1 Diabetes: Is Adjunctive Therapy the Way Forward?

Abstract

Despite advances in insulin therapies, patients with type 1 diabetes (T1DM) have a shorter life span due to hyperglycaemia-induced vascular disease and hypoglycaemic complications secondary to insulin therapy. Restricting therapy for T1DM to insulin replacement is perhaps an over-simplistic approach, and we focus in this work on reviewing the role of adjuvant therapy in this population. Current data suggest that adding metformin to insulin therapy in T1DM temporarily lowers HbA1c and reduces weight and insulin requirements, but this treatment fails to show a longer-term glycaemic benefit. Agents in the sodium glucose co-transporter-2 inhibitor (SGLT-2) class demonstrate the greatest promise in correcting hyperglycaemia, but there are safety concerns in relation to the risk of diabetic ketoacidosis. Glucagon-like peptide-1 agonists (GLP-1) show a modest effect on glycaemia, if any, but significantly reduce weight, which may make them suitable for use in overweight T1DM patients. Treatment with pramlintide is not widely available worldwide, although there is evidence to indicate that this agent reduces both HbA1c and weight in T1DM. A criticism of adjuvant studies is the heavy reliance on HbA1c as the primary endpoint while generally ignoring other glycaemic parameters. Moreover, vascular risk markers and measures of insulin resistance—important considerations in individuals with a longer T1DM duration—are yet to be fully investigated following adjuvant therapies. Finally, studies to date have made the assumption that T1DM patients are a homogeneous group of individuals who respond similarly to adjuvant therapies, which is unlikely to be the case. Future longer-term adjuvant studies investigating different glycaemic parameters, surrogate vascular markers and harder clinical outcomes will refine our understanding of the roles of such therapies in various subgroups of T1DM patients.

Report from the 4th Cardiovascular Outcome Trial (CVOT) Summit of the Diabetes & Cardiovascular Disease (D&CVD) EASD Study Group

“…However, as patients with T1DM are mainly treated with insulin, CV safety of new glucose lowering agents was only investigated in the context of T2DM. As of now, a variety of studies has started to investigate the use of glucose lowering medication typically used in T2DM, like metformin, pramlintide, GLP-1 RA, SGLT-2i and dual SGLT-1 and -2i as adjunctive therapy for T1DM, particularly in patients who have inadequate insulin control and/or are overweight [ 46 ].…”

Pharmacologic adjunctive to insulin therapies in type 1 diabetes: The journey has just begun

“…Moreover, all of these studies are considering people with T1D as an homogenous group of patients, who will overall get - or not get - benefit from adjunctive therapies[31]. It is well established that some people with autoimmune diabetes (either long-term T1D or LADA) share common pathophysiological and phenotypic features with T2D, thus, being difficult to draw the borderline between distinct diabetes types, in these cases[32].…”

Adjunct Antihyperglycemic Agents in Overweight and Obese Adults With Type 1 Diabetes

“…14 Over time, people with type 1 diabetes can develop insulin resistance, which is commonly associated with obesity and the metabolic syndrome. 4 Therefore, improving insulin sensitivity would be desirable in select patients with type 1 diabetes.…”

“…Therefore, adjunct antihyperglycemic agents that promote weight loss may provide health benefits in people with type 1 diabetes who are also overweight or obese. 4…”