DAfter 2-3 months of unsuccessful lifestyle intervention, pharmacotherapy may be administered to lower glucose levels. Diabetes treatment needs to be catered to the individual and your doctor will prescribe a treatment regimen based on your individual needs.
Initial step – after diagnosing type 2 diabetes the first step to treatment is diet, exercise, and lifestyle modification.
In 2-3 months, if the blood glucose level does not reach the target, then only pharmacotherapy is recommended. The first line of treatment is Metformin (biguanide) and its dose will be adjusted to meet the target blood glucose levels. Metformin has been used as a first-line therapy for type 2 diabetes since the 1950’s.
Metformin acts by reducing plasma glucose and lactate levels, and ultimately, reduced production of glucose.
One advantage of metformin is the fact that it can be used together with other diabetes medication, including insulin. In addition, there is evidence to suggest that metformin may be beneficial in improving cardiovascular outcomes in patients with type 2 diabetes.
Second Step – individualized management.
If the blood glucose level still has not met with the targeted range after the initial step and then treatment with Metformin fails, based upon the individual`s characteristics it is recommended to add another suitable medication for the patient.
Other pharmacotherapy includes:
The sulfonylureas (such as glimepiride) are insulin sensitizers that stimulate the secretion of insulin from the β cells in the pancreas. Sulfonylureas rapidly reduce HbA1c and glucose levels.
Sulfonylureas offer relatively good blood glucose control, however, are not good for patients who are overweight as they can result in increased body weight. In addition, treatment can result in hypoglycaemia. Gliclazide and glimepiride are less likely to result in hypoglycaemia than glyburide.
TZDs include pioglitazone, meglitinides, and repaglinide, which act to increase insulin sensitivity by increasing glucose utilization and reducing glucose production.
This group of drugs offer relatively good glycemic control, rarely occurring hypoglycaemic episodes, but tend to have more side effects. Therefore, this group of agents are not recommended for patients with heart disease. It takes approximately 6-12 weeks to achieve the maximum effect.
This class of drugs include alogliptin, linagliptin, saxagliptin, and sitagliptin. DPP-4 inhibitors prevent the action of the enzyme dipeptidyl peptidase-4, which acts to remove incretin from the body. Incretin signals the release of insulin after eating. In this way DPP-4 inhibitors result in an increase in insulin release and reduction in blood glucose.
DPP-4 inhibitors result in moderate control of blood glucose levels. Hypoglycaemia occurs rarely with minimum side effects.
GLP1 receptor agonists
Glucagon-like peptide-1 (GLP-1) receptor agonists (exenatide, liraglutide, pramlintide) are a class of injectable drugs. They act by mimicking GLP-1 which results in an increase in incretin, causing increased release of insulin.
This class of drugs have a relatively a good effect on glycemic control, and may also help to reduce weight. These medications can have side-effects on the gastrointestinal tract.
Good glycemic control can be achieved with flexible regimens. Timely adjustments to the drug regimens have to be done to obtain the target blood glucose levels within 3-6 months.
The newest group of anti diabetes drugs are SGLT-2 inhibitors (dapagliflozin, canagliflozin, empagliflozin, ipragliflozin).
SGLT2 is a protein that facilitates glucose reabsorption in the kidneys. SGLT2 inhibitors block this process increasing glucose excretion with urine, resulting in lowering blood glucose levels significantly. Since this mechanism is independent of insulin, the risk of major hypoglycemia is low.
There is some concern with the side-effect of ketoacidosis, a condition where there are high levels of ketones in the blood.
Clinical trials are underway to test this class of drugs in treating type 2 diabetes.
Madiraju AK, Erion DM, Rahimi Y, et al. “Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase.” Nature 2014;510:542–6.
Holman RR, Paul SK, Bethel MA, et al. “10-year follow-up of intensive glucose control in type 2 diabetes.” N Engl J Med 2008;359:1577–89.
Johnson JA. “The safety of sulfonylurea therapy in type 2 diabetes: have we reached the practical limits of our evidence base?” Diabetologia 2015;58:1–3.
Yki-Järvinen H. “Thiazolidinediones” New England Journal of Medicine, 2004;351(11):1106.
Cornell, S. “Continual evolution of type 2 diabetes: an update on pathophysiology and emerging treatment options” Therapeutics and Clinical Risk Management, 16 April 2015 , Volume 2015:11, Pages 621—632
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