Background: The increasing worldwide prevalence of diabetes mellitus confers heavy public health
issues and points to a large medical need for effective and novel anti-diabetic approaches with negligible adverse
effects. Developing effective and novel anti-diabetic approaches to curb diabetes is one of the most foremost
Objectives: This article aims to provide an overview of current pharmacological and non-pharmacological approaches
available for the management of diabetes mellitus.
Methods: Research articles that focused on pharmacological and non-pharmacological interventions for diabetes
were collected from various search engines such as Science Direct and Scopus, using keywords like diabetes,
glucagon-like peptide-1, glucose homeostasis, etc.
Results: We review in detail several key pathways and pharmacological targets (e.g., the G protein-coupled receptors-
cyclic adenosine monophosphate, 5′-adenosine monophosphate-activated protein kinase, sodium-glucose
cotransporters 2, and peroxisome proliferator activated-receptor gamma signaling pathways) that are vital in the
regulation of glucose homeostasis. The currently approved diabetes medications, the pharmacological potentials
of naturally occurring compounds as promising interventions for diabetes, and the non-pharmacological methods
designed to mitigate diabetes are summarized and discussed.
Conclusion: Pharmacological-based approaches such as insulin, metformin, sodium-glucose cotransporters 2
inhibitor, sulfonylureas, glucagon-like peptide-1 receptor agonists, and dipeptidyl peptidase IV inhibitors represent
the most important strategies in diabetes management. These approved diabetes medications work via targeting
the central signaling pathways related to the etiology of diabetes. Non-pharmacological approaches, including
dietary modification, increased physical activity, and microbiota-based therapy are the other cornerstones for
diabetes treatment. Pharmacological-based approaches may be incorporated when lifestyle modification alone is
insufficient to achieve positive outcomes.