Sulfonylureas with insulin

The absorption of sulfonylureas from the upper gastrointestinal tract is faidy rapid and complete. The agents are transported in the blood as protein-bound complexes. As they are released from protein-binding sites, the free (unbound) form becomes available for diffusion into tissues and to sites of action. Specific receptors are present on pancreatic islet P-ceU surfaces which bind sulfonylureas with high affinity. Binding of sulfonylureas to these receptors appears to be coupled to an ATP-sensitive channel to stimulate insulin secretion. These agents may also potentiate insulin-stimulated glucose transport in adipose tissue and skeletal muscle. 

When oral antidiabetic drug are combined with other antidiabetic drug (eg, sulfonylureas) or insulin, the hypoglycemic effect may be enhanced. Elderly, debilitated, or malnourished patients are more likely to experience hypoglycemia... 

Coadministration Acarbose given in combination with a sulfonylurea or insulin will cause a further lowering of blood glucose and may increase the hypoglycemic potential of the sulfonylurea. 

Metformin IR tablets, oral solution, or ER tablets may be used concomitantly with a sulfonylurea or insulin to improve glycemic control in adults 17 years of age and older. 

Hypoglycemia Patients receiving pioglitazone or rosiglitazone in combination with insulin or oral hypoglycemics (eg, sulfonylureas) may be at risk for hypoglycemia reduction in the dose of insulin or sulfonylureas may be necessary. 

Nephropathy in type 2 diabetes-The usual starting dose is 50 mg once daily. Increase the dose to 100 mg once daily based on blood pressure response. Losartan may be administered with insulin and other commonly used hypoglycemic agents (eg, sulfonylureas, glitazones, glucosidase inhibitors). 

Rosiglitazone is approved for use as monotherapy and in conjunction with metformin, though it is sometimes combined with a sulfonylurea or insulin. It is usually taken once or twice a day with or without food. Rosiglitazone may cause a modest increase in low-density lipoprotein and triglyceride concentrations, but it is unclear whether this effect has any clinical significance or persists in the long term. 

Diabetes mellitus, combination therapy PO With insulin Initially, 15-30 mg once a day. Initially, continue current insulin dosage then decrease insulin dosage by 10% to 25% if hypoglycemia occurs or plasma glucose level decreases to less than 100 mg/dl. Maximum 45 mg/day. With sulfonylureas Initially, 15-30 mg/day. Decrease sulfonylurea dosage if hypoglycemia occurs. With metformin Initially, 15-30 mg/day. As monotherapy Monotherapy is not to be used if patient is well controlled with diet and exercise alone. Initially, 15-30 mg/day. May increase dosage in increments until 45 mg/day is reached. 

If the patient is taking repaglinide with insulin or a sulfonylurea, always have a source of glucose available to treat symptoms of low blood sugar... 

It is a very potent sulfonylurea with long duration of action indicated in non-insulin dependent (type II) diabetes, whenever blood sugar levels can not be controlled adequately by diet, physical exercise or reduction in body weight. 

Exenatide is approved for use in individuals who fail to achieve desired glycemic control on biguanides, or biguanides plus sulfonylureas. Hypoglycemia is a risk when exenatide is used with an insulin secretagogue or with insulin. The doses of the latter drugs have to be reduced at the initiation of exenatide therapy and subsequently titrated. 

Pramlintide is approved for concurrent mealtime administration in individuals with type 2 diabetes treated with insulin, metformin, or a sulfonylurea who are unable to achieve their postprandial glucose targets. Combination therapy results in a significant reduction in early postprandial glucose excursions mealtime insulin or sulfonylurea doses usually have to be reduced to prevent hypoglycemia. 

Bedtime insulin has been suggested as an adjunct to oral antidiabetic therapy in patients with type 2 diabetes who have not responded to maximal oral therapy. Clinical practice has evolved to include sulfonylureas, meglitinides, D-phenylalanine derivatives, biguanides, thiazolidinediones, or rr.-glucosidase inhibitors given in conjunction with insulin. 

Treatment of sulfonylurea-induced hypoglycemia and of overdose with sulfonylureas has been reviewed (69). If intravenous dextrose is insufficient, octreotide is recommended (70) but not diazoxide. In patients with insulin reserve, dextrose can stimulate insulin secretion and paradoxically worsen the condition. Patients with drug-induced hypoglycemia should not be given glucagon, since it will stimulate insulin secretion. Hypoglycemia can last for up to 5 days. Continued observation is important, because recurrence after temporary recovery is common. 

Sulfonylureas (n = 68) and metformin (n = 50) have been compared retrospectively with insulin (n = 42) in pregnancy (131). There were no severe attacks of hypoglycemia, no jaundice, and no differences in neonatal morbidity. However, in those who took metformin, preeclampsia and perinatal deaths were more common. Since metformin was given to obese women, and since obesity contributes to pre-eclampsia and perinatal mortality, this may have been an effect of obesity. 

There is no indication for combining insulin with insulin secretagogues (sulfonylureas, meglitinides, or D-phenylalanine derivatives) in individuals with type 1 diabetes. Type 1 diabetics with diets very high in starch may benefit from the addition of tt-glucosidase inhibitors, but this is not typically practiced in the USA. 

Troglitazone, the first clinically available thiazolidinedione, was approved for use in patients who have failed diet therapy and, in combination with insulin and/or sulfonylureas, in patients inadequately controlled with these agents alone (117). Although studies have documented the hypoglycemic efficacy of troglitazone in patients with type 2 diabetes, its use was associated with elevated liver enzymes, liver damage, and death... 

Correct answer = C. Protamine complexes with insulin to form an insoluble complex that is slowly absorbed. Insulin is not administered orally because it is destroyed by proteases in the Gl tract. Diet therapy and/or sulfonylureas are often effective without additional insulin In the therapy of Type II diabetics. Ketoacidosis is the most life-threatening consequence of Type I diabetics and requires adequate treatment with insuiin, not sulfonylureas. Insulin acts by binding to specific receptors in the cell membrane, not in the nucleus. 

Glimepiride [gly MEH pih ride] is a new, second generation sulfonylurea. It was the first sulfonylurea to be approved for concurrent use with insulin, but has no additional advantage over the other sulfonylureas. Elimination is through the urine and feces. Like all sulfonylureas, it can cause hypoglycemia, hyperinsulinemia, and weight gain. 

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