Pharmacotherapy in Type 2 Diabetes Mellitus

November 14 2017 at 06:42 AM by Admin

Type 2 diabetes is the most commonly observed phenomena in the recent times.Type 2 diabetes mellitus and associated cardiovascular diseases are major contributors to this disease burden leading to rising morbidity and mortality. Type 2 diabetes with its micro and macrovascular complications is occurring in younger populations all around the world. It is thus appropriate to incorporate preventive strategies to reduce the burden of this disease. Along with inculcating healthy lifestyle habits across populations, it may be suitable to use preventive pharmacotherapy in those suffering from diabetes.

Causes of Type 2 Diabetes

Type 2 diabetes is a condition in which cells cannot use blood sugar efficiently for energy. This happens when the cells become insensitive to insulin and the blood sugar gradually gets too high. Some of the broad categories of causes of type 2 diabetes include -

  • Obesity
  • Consuming artificial sweeteners
  • Lack of exercise
  • Stress
  • Genetics

Pharmacotherapy for Prevention of Type 2 Diabetes

The history of pharmacological interventions for prevention goes a long way back. Pharmacotherapy is a therapy using pharmaceutical drugs, as distinguished from therapy using surgery, radiation, movement or other modes. Over the years there has been tremendous progress in the pharmacotherapy of diabetes, particularly type 2 diabetes.Early initiation of pharmacologic therapy is associated with improved glycemic control and reduced long-term complications in type 2 diabetes. Drug classes used for the treatment of type 2 diabetes include the following:


  • Biguanides -Metformin is the only biguanide in clinical use. Another biguanide, phenformin, was taken off the market in the United States in the 1970s because of its risk of causing lactic acidosis and associated mortality (rate of approximately 50%). Metformin has proved effective and safe.


  • Sulfonylureas - Sulfonylureas (eg, glyburide, glipizide, glimepiride) are insulin secretagogues that stimulate insulin release from pancreatic beta cells and probably have the greatest efficacy for glycemic lowering of any of the oral agents.


  • Meglitinide derivatives - Meglitinides (eg, repaglinide, nateglinide) are much shorter-acting insulin secretagogues than the sulfonylureas are, with preprandial dosing potentially achieving more physiologic insulin release and less risk for hypoglycemia. [135]Although meglitinides are considerably more expensive than sulfonylureas, they are similar in their glycemic clinical efficacy.


  • Alpha-glucosidase inhibitors - These agents delay sugar absorption and help to prevent postprandial glucose surges. Alpha-glucosidase inhibitors prolong the absorption of carbohydrates, but their induction of flatulence greatly limits their use. They should be titrated slowly to reduce gastrointestinal (GI) intolerance.



  • Thiazolidinediones (TZDs) - TZDs (eg, pioglitazone [Actos], rosiglitazone [Avandia]) act as insulin sensitizers; thus, they require the presence of insulin to work. They must be taken for 12-16 weeks to achieve maximal effect.


  • Glucagonlike peptide–1 (GLP-1) agonists - GLP-1 agonists (ie, exenatide, liraglutide, albiglutide, dulaglutide) mimic the endogenous incretin GLP-1; they stimulate glucose-dependent insulin release, reduce glucagon, and slow gastric emptying.


  • Dipeptidyl peptidase IV (DPP-4) inhibitors - DPP-4 inhibitors (eg, sitagliptin, saxagliptin, linagliptin) are a class of drugs that prolong the action of incretin hormones.


  • Selective sodium-glucose transporter-2 (SGLT-2) inhibitors - Canagliflozin is the first SGLT-2 inhibitor approved in the United States. [173, 174]SGLT-2 inhibition lowers the renal glucose threshold (ie, the plasma glucose concentration that exceeds the maximum glucose reabsorption capacity of the kidney). Lowering the renal glucose threshold results in increased urinary glucose excretion. 


  • Insulins - Ultimately, many patients with type 2 diabetes mellitus become markedly insulinopenic. The only therapy that corrects this defect is insulin. Because most patients are insulin resistant, small changes in insulin dosage may make no difference in glycemia in some patients. Furthermore, because insulin resistance is variable from patient to patient, therapy must be individualized for each patient.


  • Amylinomimetics - Pramlintide acetate is an amylin analog that mimics the effects of endogenous amylin, which is secreted by pancreatic beta cells. This agent delays gastric emptying decreases postprandial glucagon release and modulates appetite.


  • Bile acid sequestrants - Bile acid sequestrants were developed as lipid-lowering agents for the treatment of hypercholesterolemia but were subsequently found to have a glucose-lowering effect. The bile acid sequestrant colesevelam is FDA-approved as an adjunctive therapy to improve glycemic control.


  • Dopamine agonists - In 2009, the FDA approved a quick-release formulation of bromocriptine mesylate (Cycloset) as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Bromocriptine is a centrally acting dopamine D2 receptor agonist. When given in a single timed morning dose, it is thought to act on circadian neuronal activities within the hypothalamus to reset the abnormally elevated drive for increased plasma glucose, triglyceride, and free fatty acid levels in fasting and postprandial states in insulin-resistant patients.