T2D Therapy and Management

T2D Therapy and Management

Intensive lifestyle modification, pharmacology (drug treatment) or both can reverse, delay or prevent type 2 diabetes. The main treatment for T2DM is healthy lifestyle adopting a healthy diet, increased physical activity, smoking cessation and maintenance of health body weight. 

Management of obesity: 60% of patients with type 2 diabetes are obese (body-mass index [BMI] ≥30) and show insulin resistance. Obesity is addressed by lifestyle modification, although  drug therapy, very low calorie diets, and bariatric surgery might also be considered.

If attempts to change lifestyle are inadequate to manage blood glucose levels oral medication is initiated with metformin the most common with the exception of contraindications such as renal impairments. Multiple drug combinations may be used for the management of the blood glucose levels of Type 2 Diabetics inclusive of GLP-1 agonists, SGLT2 inhibitors, DPP4 inhibitors, sulphonyl ureas, thiazolidinediones and alpha-glucosidase inhibitors.

Metformin: Metformin reduces hepatic glucose output, enhances peripheral tissue sensitivity, and stimulates GLP-1 secretion. Furthermore, metformin effectively lowers HbA1c concentration by about 1–2%, is weight neutral, does not cause hypoglycaemia, and can have modest beneficial effects on blood pressure and lipid profile.

GLP-1 agonists: GLP-1 agonists trigger GLP-1-like effects, which include increased insulin secretion, reduced glucagon secretion, reduced hepatic glucose output, delayed gastric emptying, and increased satiety ( feeling of fullness). GLP-1 receptor agonists are either long-acting (dulaglutide, albiglutide, liraglutide) or short-acting (exenatide, lixisenatide) drugs that are given once weekly or once or twice daily. This class of drugs is effective, with reductions in HbA1c concentration of about 1% and weight loss of up to 4 kg. The risk of hypoglycaemia is low unless combined with sulfonylureas or insulin.

SGLT-2 inhibitors (dapagliflozin, canagliflozin, empagliflozin) are the latest glucose-lowering agents to become available. These drugs increase urinary glucose excretion by inhibiting SGLT-2 in the renal proximal tubule. These drugs do not cause hypoglycaemia (too low blood glucose) unless combined with sulfonylureas or insulin.

Dipeptidyl peptidase-4 inhibitors (gliptins): DPP-4 inhibitors are oral agents that inhibit activity of the enzyme DPP-4 and hence prolong the actions of endogenous GLP-1. Three DPP-4 inhibitors are currently available: sitagliptin, vildagliptin and saxagliptin. all been shown to be effective at lowering HbA1c by nearly 0.7 to 1%.

Sulfonylureas, such as gliclazide and glimepiride, act on β cells to stimulate insulin secretion and, as a consequence of established efficacy and low cost, are often the first choice for dual therapy. However, these drugs are associated with hypoglycaemia (up to six times increased risk compared with metformin) and weight gain, and concerns remain with respect to an association with adverse cardiovascular disease outcomes.

Bariatric Surgery is emerging as a successful option for the treatment of obesity and type 2 diabetes. There is accumulating evidence that surgery with gastrointestinal manipulations may result in T2DM remission. Bariatric surgery has been shown to improve glucose homeostasis (stable steady level) by reducing insulin resistance and increasing insulin secretion.