Hypoglycemic Potential of Current and Emerging Pharmacotherapies in Type 2 Diabetes Mellitus

Abstract

Intensive glycemic control can reduce the risk of microvascular complications in patients with type 2 diabetes mellitus (T2DM). However, hypoglycemia induced by diabetes medications is recognized as a major limiting factor in the attainment of glycemic goals. Mild hypoglycemia is relatively common in patients with T2DM, and the prevalence of severe hypoglycemia increases with insulin treatment and can approach the prevalence seen in patients with type 1 diabetes. Mild hypoglycemia and the fear of hypoglycemia can have a substantial impact on the physical, mental, social, and economic well-being of patients with T2DM. Severe hypoglycemia is more serious and may be associated with an increased risk of dementia, cardiovascular events, and death. Insulin and insulin secretagogue therapies (eg, sulfonylureas and meglitinides) are the major causes of hypoglycemia in patients with T2DM. Other diabetes drugs, such as metformin, when used as monotherapy, have a low risk of hypoglycemia. Emerging experimental therapies, such as activators of the free fatty acid receptor 1, G protein-coupled receptor 119 agonists, glucokinase activators, inhibitors of 11β-hydroxysteroid dehydrogenase type 1, and sodium-glucose co-transporter 2 inhibitors, some of which have mechanisms of action consistent with a potential low risk of hypoglycemia, may help patients with T2DM achieve improved glycemic control.

Urinary tract and genital infections in patients with type 2 diabetes treated with sodium‐glucose co‐transporter 2 inhibitors: A meta‐analysis of randomized controlled trials

“…Type 2 diabetes mellitus (T2DM) is a complex progressive metabolic disorder associated with macrovascular and microvascular complications, which has already become the leading cause of death and disability worldwide . In addition to lifestyle management, oral antidiabetic drugs (OADs), including metformin, sulphonylureas and thiazolidinediones, are of great importance for the pharmacological treatment of T2DM; however, therapeutic strategies that improve either insulin secretion or insulin sensitivity are always associated with gradual loss of efficacy over time owing to the progressive loss of β‐cell function and to metabolic comorbidities such as obesity, hypoglycaemia and heart failure …”

Improved glycaemic control and lower hypoglycaemia risk with reduced prior oral antidiabetes drug therapy in patients with type 2 diabetes treated with insulin glargine 300 U/mL

“…15 On the other hand, however, discontinuing other classes of OAD with different mechanisms of action may reduce the possibilities to further decrease HbA1c levels and modify noninsulin-dependent physiological targets. 14 However, there is a surprising shortage of relevant data regarding this phenomenon, perhaps because it may be considered counterintuitive to reduce the overall therapeutic burden in a disease that is complex and progressive.…”

Cardiovascular safety of type 2 diabetes medications: Review of existing literature and clinical implications

“…The main side effects insulin are hypoglycemia and weight gain, while severe hypoglycemia can increase the risk of dementia, CV events and death. 13 …”