Diabetes is a chronic debilitating illness high blood sugar levels can cause serious damage to the heart, eyes, blood vessels, kidneys and nerves. It is a silent killer initially as it might not give obvious symptoms so that you cannot identify it unless a blood sugar test is done . Although type 2 diabetes can often be at least partially controlled by a healthy diet and regular exercise currently there is no cure for diabetes. In addition to lifestyle modifications and diet medications are use to control the blood sugar levels more successfully . We called them antihyperglycemic medications. Until recently we had a limited number of treatment options including sulphonylurea and Biguanides (metformin).

However with the advent of new medications we have more hopes and development in diabetes management process to avoid disabling or life threatening complications.

The article is attempt to discuss the different types of medications which can be used for individual patients with various comorbidities.

1  Sulfonylureas potently lower blood glucose level through their ability to promote the secretion of insulin from pancreatic β cells .However, they have often been shown to be associated with the side effect of hypoglycaemia, weight gain in patients who are less adherent to MNT and/or physical activity/exercise. anorexia, nausea, diarrhoea, skin rashes, occasionally blood dyscrasias

Glibenclamide and glimepiride may cause high rates of hypoglycaemia (in older patients and in patients with autonomic neuropathy or nephropathy).

2 Biguanides (Metformin) are currently used as first-line glucose-lowering agents. Biguanides exert their effect by inhibiting hepatic glucose production as well as by improving peripheral insulin sensitivity. Current evidence demonstrates their usefulness in reducing macroangiopathy in patients with type 2 diabetes. should be used with caution in people with hepatic or cardiac disease, and thosewith a heavy alcohol intake or dehydration (eg acute gastroenteritis) and renal impairment due to risks of lactic acidosis. It is contraindicated in EGFR less than 30.

Side effects includes anorexia, nausea, vomiting,  diarrhoea, abdominal cramps, flatulence

lactic acidosis (uncommon, but may occur with dehydration and co-existing renal, liver or cardiovascular disease [CVD]), possible vitamin B12 deficiency.

3 α-Glucosidase inhibitors ( Acarbose) , which inhibit intestinal glycolysis  and delay intestinal glucose absorption, suppress postpran- dial hyperglycemia and hyperinsulinemia and should be  taken immediately before meals; they are also often associated with flatus and diarrhea. Hypoglycemia in patients  treated with these agents can be effectively improved with  the ingestion of only glucose.

4  Thiazolidinediones improve glycemic control by promoting peripheral insulin sensitivity and inhibiting hepatic glucose release; they are also often associated with weight gain due to their ability to promote fluid retention and adipocyte differentiation. Patients receiving Thiazolidinediones require monitoring for edema, anemia and fracture associated with the use of Thiazolidinediones. It is contraindicated in moderate to severe cardiac failure (pioglitazone and rosiglitazone) also believed to be  increased risk of bladder cancer.

Incretins –Two classes of incretin medications exist – dipeptidyl peptidase-4 inhibitor (DPP-4i) and glucagon-like peptide-1 receptor agonist (GLP-1 RA).

5 . DPP-4 inhibitors glucose-dependently promote post-prandial insulin secretion while at the same time inhib-iting glucagon secretion, thus improving both fasting and postprandial hyperglycemia. While the risk of hypoglycemia with DPP-4 inhibitor monotherapy is small, combination therapy with an SU or insulin increases the risk of hypoglycaemia so that monitoring is required , DPP-4 inhibitors were previously thought to be associ-ated with the risk of acute pancreatitis, pancreatic cancer or infections; however, current evidence appears to argue against this . dose reduction in renal impairment eGFR <60 mL/min/1.73 m2 for alogliptin, saxagliptin, sitaglitpin, and vildagliptin. However linagliptin can be safely use till EGFR down to 30. Main side effects: are nasopharyngitis, headache,  upper respiratory tract symptoms.

6 Glucagon like peptide inhibitor  GLP-1 RA includes exenatide, liraglutide and lixisenitide. GLP-1  promote postprandial insulin secretion in a glucose-dependent manner while at the same time inhib-iting glucagon secretion; It causes  weight loss through actions on cerebral hormonal responses to insulin and appetite may affect gastric emptying. Side effects includes nausea, vomiting ,pancreatitis (rarely) and weight loss.

7 SGLT2 inhibitors inhibit glucose reabsorption in the proximal renal tubule and promote urinary glucose excretion, thus exerting their glucose-lowering effect; they not only improve glycemic control independently of insulin-mediated mechanisms but also associated with body weight reduction.The main  Side effects includes  weight loss, increased urogenital mycotic and urinary tract infections, aggravate dehydration . A few cases of euglycaemic diabetic ketoacidosis (DKA) were also reported.

Now we have more chances to select more appropriate medications in your individual patients based on their other physical and psychosocial factors .Currently there are researches for new groups of medications and other procedures including beta stem cell transplant are under experimental with promising results . So that we have potential brighter future in diabetes management . Reference Diabetes Foundation Australia Guidlines )

Pubudu Jayaweera



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