One hundred years since insulin discovery: An update on current and future perspectives for pharmacotherapy of diabetes mellitus

Abstract

Diabetes mellitus was considered a fatal malady until the discovery, extraction and commercial availability of insulins. Numerous other classes of drugs ranging from sulfonylureas to sodium‐glucose co‐transporter‐2 inhibitors were then marketed. However, with the prevalence of diabetes mellitus increasing every year, many more drugs and therapies are under investigation. This review article aimed to summarize the significant developments in the pharmacotherapy of diabetes mellitus and outline the progress made by the recent advances, 100 years since insulins were first extracted successfully. Insulin analogues and insulin delivery pumps have further improved glycaemic control in diabetes mellitus. Cardiovascular and renal outcome trials have changed the landscape of diabetology, with some of these drugs also efficacious in nondiabetics. Newer drug delivery systems are being evaluated to improve the efficacy and reduce the dosing frequency and adverse effects of antidiabetics. Some newer drugs with novel mechanisms of action targeting type 1 and type 2 diabetes have also shown promise in recent clinical trials. These drugs include dual glucose‐dependent insulinotropic polypeptide and glucagon‐like peptide 1‐agonists, glucokinase activators, anti‐CD3 monoclonal antibodies and glimins. Their efficacy needs to be evaluated in larger studies.

Metabolic, structural and biochemical changes in diabetes and the development of heart failure

“…New drugs in the pipeline for the treatment of diabetes that need to be assessed for their effects on CVD include, but are not limited to, dual gastric inhibitory polypeptide and GLP-1 receptor agonist, glimins (e.g. Imeglimin), anti-CD3 monoclonal antibody and sparc-related modular calcium-binding protein 1 [100]. Overall, it is important to note that, regardless of the drug used to treat a patient with both diabetes and heart failure, systemic metabolism will influence cardiac metabolism and as such, efforts to improve whole-body systemic metabolism via lifestyle changes (i.e.…”

Drug-induced mitochondrial toxicity: Risks of developing glucose handling impairments

“…were related to DM in 2021. Most cases of diabetes fall into two broad etiopathogenetic categories, these include type 1 and type 2 diabetes (1)(2)(3). Type 1 diabetes mellitus (T1DM) is insulin-dependent and develops because of pancreatic beta-cell destruction which leads to insufficient insulin secretion.…”

“…Type 1 diabetes mellitus (T1DM) is insulin-dependent and develops because of pancreatic beta-cell destruction which leads to insufficient insulin secretion. Type 2 (T2DM) which is also known as Non-Insulin Dependent Diabetes Mellitus (NIDDM), or adult-onset diabetes is prevalent (1)(2)(3). Often, the development of T2DM is attributed to the inability of insulin-sensitive cells to respond to insulin (1)(2)(3).…”

“…Type 2 (T2DM) which is also known as Non-Insulin Dependent Diabetes Mellitus (NIDDM), or adult-onset diabetes is prevalent (1)(2)(3). Often, the development of T2DM is attributed to the inability of insulin-sensitive cells to respond to insulin (1)(2)(3). According to clinical and non-clinical studies, T2DM accounts for approximately 90% of diabetes cases.…”

“…According to clinical and non-clinical studies, T2DM accounts for approximately 90% of diabetes cases. The risk factors of T2DM include obesity, age, epigenomics, and lifestyle patterns (1)(2)(3).…”