For patients trying to achieve near euglycemia, premeal glucose values of 4.5-6.5 mmol/dl are the goal, with bedtime value at least 5.5mmol/dL. In patients with less stringent glycemic goals (eg, because of advanced age, advanced complications, or severe concomitant disease), preprandial glucose values of 5.5-7.8 mmol/dL are desired.
Although the long-term benefits and harms of diabetes medications remain unclear, the evidence supports the use of metformin as a first-line agent. Metformin has shown to significantly improve hemoglobin A1c and lipid profile. It is the only oral diabetes drug that reliably facilitates modest weight loss.
Improvements in body weight, glycemic control, and insulin requirements, support continuing metformin treatment after the introduction of insulin in patients with type 2 diabetes mellitus
Epidemiological studies have found that patients treated with metformin had better overall and cancer-specific survival than those treated with other types of glucose-lowering agents.
Even though sulfonylureas are safer in general, within the group, the use of glibenclamisehas been associated with the highest mortality compared with other sulfonylureas.
Meglitinide derivatives (eg, repaglinide, nateglinide) are much shorter-acting insulin secretagogues compared to sulfonylureas which allows premeal dosing with less risk for hypoglycemia
Alpha-glucosidase inhibitors(Acarbose, Miglitol andVoglibose)should be titrated slowly to reduce gastrointestinal (GI) intolerance
Although the peak effect of thiazolidinediones(eg, pioglitazone , rosiglitazone) is delayed (takes 12-16 weeks), they are the only antidiabetic agents that have been shown to delay the progression to frank diabetes. However, this class is associated with significant edema (including macular edema) and weight gain. Long term use is also strongly associated with increased fracture risk (pioglitazone)and anelevated risk of myocardial infarction (Rosiglitazone)
Glucagonlike peptide–1 agonists (ieexenatide, liraglutide, albiglutide, dulaglutide) produces a modest weight loss when combined with metformin and/or a sulfonylurea. They also prevent beta-cell apoptosis, and in time restore beta-cell function. Adverse effects included nausea, diarrhea, vomiting, abdominal pain, and decreased appetite
Liraglutide is indicatedfor risk reduction of major cardiovascular events (cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke) in adults with type 2 diabetes mellitus and established cardiovascular disease.
Dulaglutide is not recommended for use as first-line treatment, and it is contraindicated in patients with personal or family history of endocrine diseases (egmedullary thyroid carcinoma)
Upper respiratory tract infections have been increasingly reported among users of DPP-4 inhibitors(eg, sitagliptin, saxagliptin, linagliptin) but could reduce the risk of bone fractures.
linagliptin has predominantly non–renal excretion and is a clinically nonrelevant substrate for cytochrome-450 isoenzymes;thus, has low risk of drug-drug interaction and potentially safe in renal insufficiency.
Dosage adjustments are required for canagliflozin (SGLT-2 inhibitors) in patients who have renal impairment (ie, estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m2).
In late 2016, the FDA approved empagliflozin (SGLT-2 inhibitors)for the prevention of cardiovascular disease–related death in adults with type 2 diabetes who also have cardiovascular disease
Dual-drug therapyis indicated if the patient fails to safely achieve or sustain glycemic goals within 2-3 months. Failure of initial therapy usually should result in addition of another class of drug rather than substitution (unless due to drug intolerance)
The choice of the 2nd drug should be guided by patient characteristics, for example, DPP-4 inhibitor if both postprandial and fasting glucose levels are elevated; GLP-1 agonist if postprandial glucose levels are strongly elevated; thiazolidinediones, if the patient has metabolic syndrome and/or nonalcoholic fatty liver disease
If 2 drugs prove unsuccessful after 2-3 months. The third drug may be an oral agent from a third class of antidiabetic drugs; basal insulin (typically at bedtime).
If a regimen combining oral agents and insulin fails to lower glucose levels into the normal range, patients should be switched to a daily multiple-injection schedule with a premeal rapid-acting insulin and a longer-acting basal insulin.The basal insulin can then be titrated to the morning sugar, and the bolus premeal insulin can be titrated to the next premeal sugar and, in some cases, a postprandial (2 h) value.
To succeed a regimented lifestyle, with mealtimes regularly spaced and insulin injections taken at essentially the same time every day, including weekends and holidays is necessary.
HbA1c is measured at least twice yearly in stable patients meeting treatment goals and quarterly in unstable patients not meeting treatment goals.
Glycemic targets varies within and across countries the and institutions. HbA1c target varies from 7% bythe American College of Physicians to 6.5% by the International Diabetes Federation. Target, however, must be individualized in cases of advanced age, presence of comorbidities. In the very aged (life expectancy< 5 years) tight control may be unnecessary, whereas patients with cardiovascular or cerebrovascular disease may need higher fasting glucose targets (eg, 100-150 mg/dL) to prevent severe hypoglycemia.
It has been shown that treatment with antihypertensive medications taken at bedtime provides better ambulatory blood pressure control, as well as significant reduction in cardiovascular morbidity and mortality when compared with taking medications upon waking.
Vasoconstricting beta blockers (pindolol, penbutolol and acebutolol), unlike the vasodilating beta blocker carvedilol, are associated with decreased HDL cholesterol levels and elevated triglyceride levels.
Use of statins (atorvastatin, lovastatin, simvastatin) is effective for primary and secondary prevention of coronary heart disease (CHD) events in patients with diabetes
Patients with diabetes who are at high risk for cardiovascular events should receive low-dose, enteric-coated aspirin or clopidogrel (in aspirin intolerance)
Autonomic neuropathy may manifest as orthostatic hypotension. Such patients may require volume expanders or adrenergic agents. Patients with cystopathy(classic triad of symptoms: decreased bladder sensation, increased bladder capacity, and impaired detrusor contractility) may benefit from cholinergic agents.
Patients with intercurrent illness become more insulin resistant because of the effects of increased counterregulatory (ie, anti-insulin) hormones. Therefore, despite decreased nutritional intake, glycemia may worsen. Patients on oral agents may need transient therapy with insulin to achieve adequate glycemic control.
However, ill patients taking metformin that leads to dehydration or hypoperfusion, the drug should be temporarily discontinued because of a possible increased risk of lactic acidosis.
For patients who require more prolonged periods without oral nutrition and for major surgery, constant infusion IV insulin is preferred. Metformin is temporarily discontinued after any major surgery until the patient is clearly hemodynamically stable and normal renal function is documented. #Thursdaybit3