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1. Metformin is the drug of choice for initiating insulin in most patients with Type 2 diabetes. Metformin can be started straight away at the time of diagnosis of diabetes, along with advice on diet and lifestyle modification. It should be started in a low dose to avoid gastric discomfort and the dose should then be gradually increased. The full effect of Metformin will take two to three weeks to manifest and so, dose increases should not be done more frequently than every two weeks. Metformin should not be used in those clinical situations where there is poor tissue perfusion, as for example, in refractory congestive cardiac failure. This is because of the increased risk of lactic acidosis. Mild impairment of renal function (Grades 1 and 2 chronic kidney disease) is not a contraindication for Metformin.

2. The second drug used for control of blood sugar when Metformin alone is insufficient is usually a sulphonylurea like Gliclazide, Glibenclamide or Glimipiride. These drugs vary in their duration of action. Long acting sulphonylureas like Glibenclamide and Glimipiride have a greater risk of causing hypoglycemia in patients with renal impairment. Sulphonylureas are very effective in lowering glucose levels in the blood but, apart from their tendency to cause hypoglycemia, these drugs may have an adverse effect on the beta cells of the pancreas when used in high doses for prolonged periods. Because of this tendency to cause beta cell failure, it is not advisable to use high doses of sulphonylureas for too long. Instead, it is better to introduce insulin (or another drug) for therapy when it becomes apparent that near maximal doses of sulphonylureas are ineffective in achieving target levels of plasma glucose. The other classes of oral hypoglycemic drugs that can be used are:

Glinides (example, Repaglinide)
Alpha glucosidase inhibitors (example, Acarbose)
Thiazolidinediones (example, Pioglitazone and Rosiglitazone)

3. If you are asked: "When is the appropriate time to initiate insulin in a patient with Type 2 diabetes?", you can answer,"Not too early, Not too late!"

"Not too early" because initiating insulin too early in a patient with Type 2 diabetes increases the risk of hypoglycemia. "Not too late" because delay in achieving good control of plasma glucose will lead to widespread non-enzymatic glycosylation of cellular proteins and irreversible organ dysfunction.

The HbA1c is a good parameter for deciding when to initiate long term insulin for a patient with Type 2 diabetes. A HbA1c of more than 10 percent at any time during treatment with oral agents suggests that insulin will be needed for good control. Also, if the HbA1c is more than 8.5 percent with appropriate doses of two oral hypoglycemic agents, insulin should be considered as necessary for good control.

Insulin should be initiated in Type 2 diabetes as part of the BIDS regimen. This means that a small dose of basal insulin (a long acting insulin) - usual starting dose is 0.2 units per kg body weight - is given once a day (usually bedtime or before dinner) along with oral hypoglycemic agents.
When insulin is introduced, it is safer to stop, or reduce the dose of, those sulphonylurea drugs that the patient may be already on. This is to avoid inadvertent hypoglycemia. Whatever dose of Metformin the patient is already on can generally be continued.

4. Read about the increasing role of Gliptins as first line agents: Gliptins in the treatment of diabetes.



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