Nashville Diabetes Dentist

There are several drugs available for type 2 diabetics—most are unsuitable or even dangerous for use by type 1 diabetics. They fall into several classes and are not equivalent, nor can they be simply substituted one for another. All are prescription drugs.

One of the most widely used drugs now used for type 2 diabetes is the biguanide metformin; it works primarily by reducing liver release of blood glucose from glycogen stores and secondarily by provoking some increase in cellular uptake of glucose in body tissues. Both historically, and currently, the most commonly used drugs are in the Sulfonylurea group, of which several members (including glibenclamide and gliclazide) are widely used; these increase glucose stimulated insulin secretion by the pancreas and so lower blood glucose even in the face of insulin resistance.

Newer drug classes include:

• Thiazolidinediones (TZDs) (rosiglitazone, pioglitazone, and troglitazone — the last, as Rezulin, was withdrawn from the US market because of an increased risk of systemic acidosis). These increase tissue insulin sensitivity by affecting gene expression
• α-glucosidase inhibitors (acarbose and miglitol) which interfere with absorption of some glucose containing nutrients, reducing (or at least slowing) the amount of glucose absorbed
• Meglitinides which stimulate insulin release (nateglinide, repaglinide, and their analogs) quickly; they can be taken with food, unlike the sulfonylureas which must be taken prior to food (sometimes some hours before, depending on the drug)
• Peptide analogs which work in a variety of ways:
  • Incretin mimetics which increase insulin output from the beta cells among other effects. These includes the Glucagon-like peptide (GLP) analog exenatide, sometimes referred to as lizard spit as it was first identified in Gila monster saliva
  • Dipeptidyl peptidase-4 (DPP-4) inhibitors increase Incretin levels (sitagliptin) by decreasing their deactivation rates
  • Amylin agonist analog, which slows gastric emptying and suppresses glucagon (pramlintide)

Oral

A systematic review of randomized controlled trials found that metformin and second-generation sulfonylureas are the preferred choices for most with type 2 diabetes, especially those early in the course of the disease. Failure of response after a time is not unknown with most of these agents: the initial choice of anti-diabetic drug has been compared in a randomized controlled trial which found “cumulative incidence of monotherapy failure at 5 years to be 15% with rosiglitazone, 21% with metformin, and 34% with glyburide”. Of these, rosiglitazone users showed more weight gain and edema than did non-users. Rosiglitazone may increase risk of death from cardiovascular causes though the causal connection is unclear. Pioglitazone and rosiglitazone may also increase the risk of fractures.

For patients who also have heart failure, metformin may be the best tolerated drug.

The variety of available agents can be confusing, and the clinical differences among type 2 diabetics compounds the problem. At present, choice of drugs for type 2 diabetics is rarely straightforward and in most instances has elements of repeated trial and adjustment.

Injectable peptide analogs

DPP-4 inhibitors lowered A1c by 0.74%, comparable to other antidiabetic drugs. GLP-1 analogs resulted in weight loss and had more gastrointestinal side effects, while DPP-4 inhibitors were weight neutral and increased risk for infection and headache, but both classes appear to present an alternative to other antidiabetic drugs.

Insulin

In rare cases, if antidiabetic drugs fail (ie, the clinical benefit stops), insulin therapy may be necessary – usually in addition to oral medication therapy – to maintain normal or near normal glucose levels.

Typical total daily dosage of insulin is 0.6 U/kg. But, of course, best timing and indeed total amounts depend on diet (composition, amount, and timing) as well the degree of insulin resistance. More complicated estimations to guide initial dosage of insulin are:

• For men, [(fasting plasma glucose [mmol/liter]–5)x2] x (weight [kg]÷(14.3xheight [m])–height [m])
• For women, [(fasting plasma glucose [mmol/liter]–5)x2] x (weight [kg]÷(13.2xheight [m])–height [m])

The initial insulin regimen is often chosen based on the patient’s blood glucose profile. Initially, adding nightly insulin to patients failing oral medications may be best. Nightly insulin combines better with metformin than with sulfonylureas. The initial dose of nightly insulin (measured in IU/d) should be equal to the fasting blood glucose level (measured in mmol/L). If the fasting glucose is reported in mg/dl, multiply by 0.05551 to convert to mmol/L.

When nightly insulin is insufficient, choices available are:

• Premixed insulin with a fixed ratio of short and intermediate acting insulin; this tends to be more effective than long acting insulin, but is associated with increased hypoglycemia. Initial total daily dosage of biphasic insulin can be 10 units if the fasting plasma glucose values are less than 180 mg/dl or 12 units when the fasting plasma glucose is above 180 mg/dl”. A guide to titrating fixed ratio insulin is available.
• Long acting insulins such as insulin glargine and insulin detemir. A meta-analysis of randomized controlled trials by the Cochrane Collaboration found “only a minor clinical benefit of treatment with long-acting insulin analogues for patients with diabetes mellitus type 2″.More recently, a randomized controlled trial found that although long acting insulins were less effective, they were associated with reduced hypoglycemic episodes.
• Insulin Pump therapy in Type 2 diabetes is gradually becoming popular. In an original published study, in addition to reduction of blood sugars, there is evidence of profound benefits in resistant neuropathic pain and also improvements in sexual performance.

If you’d like to receive a copy of Dr. Weaver’s FREE Diabetes Dentist Guide, sign up here!

First Name: Last Name: Email Address:

Address: City: State: Zipcode: Phone (Optional):