1.1 A

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. In the past, a second drug used for control of blood sugar when Metformin alone was insufficient used to be a sulphonylurea like Gliclazide, Glibenclamide or Glimipiride in the past. 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.

Current guidelines (2018) for introducing a second drug in therapy of diabetes requires us to look at the patient profile.
A. If the patient has atherosclerotic cardiovascular disease or heart failure, an SGLT2 inhibitor (example: canaglifozin) is preferred
B. If the patient has albuminuric CKD, an SGLT2 inhibitor is again the first choice. An injectable GLP- RA (example: liraglutide and dulaglutide) can also be considered.
C. If the patient is obese, SGLT2 inhibitors and GLP-RA are again the recommended choices
D. For achieving glycemic targets alone, a DPP4 inhibitor (example: sitagliptine) can be added to Metformin or after adding any of the above drugs. Only when cost is an issue, sulphonylureas or thiazolidinediones are to be considered as choices for reducing hyperglycemia. Even though insulin is a very potent glucose-reducing drug, the current advice is to consider an injectable GLP -RA before insulin is chosen.


3. The HbA1c is a good parameter for deciding when to initiate an injectable agent for achieving glycemic targets. As a general rule, glycemic targets for most patients is a value of HbA1c less than 7 percent. In some younger patients, the goal can be less than 6.5%. For older adults and those with multiple comorbidities, a value of less than 8 to 8.5% may be adequate. As a rule of thumb, a value of HbA1c more than 10 percent at any time during treatment with oral agents suggests that an injectable drug like insulin or GLP-RA will be needed 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, changes to the dosage of oral medicines may have to be made to avoid increased risk of hypoglycemia.


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