Drugs That Can Worsen Diabetes Control





Where the problems occur


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Thiazide diuretics






The risk of developing diabetes while taking a thiazide diuretic was also evaluated in the Nurses’ Health Study I and II as well as the Health Professionals Follow-Up Study. Between the two studies, a total of 74,816 people who initially did not have diabetes were evaluated. Over the course of treatment with a thiazide diuretic, the risk of developing diabetes was 20% higher in older women (average age 62), 51% higher in younger women (average age 40), and 31% higher in men compared to those in the studies not taking a thiazide diuretic. However, there is evidence that when hypokalemia (low blood potassium) in these people is corrected, blood glucose control improves.

The takeaway message is that thiazide diuretics are considered a good first choice for treatment of high blood pressure because they are effective, cause few side effects, and are inexpensive, but certain individuals may develop diabetes or experience difficulty controlling blood glucose while on a thiazide diuretic. Potassium levels should be monitored and corrected when necessary.


Beta-blockers are the other major class of blood-pressure-lowering drugs that have been implicated in causing diabetes or worsening diabetes control. The several large studies that have looked at the risk of diabetes associated with beta-blockers include the Nurses Health Studies I and II and the ongoing ARIC (Atherosclerosis Risk in Communities) study. In these two studies, the risk of developing diabetes in people originally without it who took beta-blockers was approximately 20% to 28% greater than in those who did not take beta-blockers.

This may seem counterintuitive since people with diabetes are often warned that beta-blockers can cause problems with low blood glucose, not high blood glucose. Beta-blockers cause these two problems in distinct ways. First, they may harm a person’s ability to recognize and respond to low blood glucose, mainly by keeping the heart rate slow, which can dampen symptoms of hypoglycemia. They may also inhibit the release of glucose from the liver. But beta-blockers also block the release of insulin by interacting with nerve signals to the pancreas and can thus lower insulin levels even when blood glucose is high.

There is some evidence that not all beta-blockers affect insulin secretion. Beta-blockers work by interacting with proteins in the body called beta receptors. There are several distinct types of beta receptors in the body. Beta-1 receptors are predominantly in the heart, while beta-2 receptors are in the heart as well as the arteries, muscles, liver, and pancreatic beta cells. This means that beta-1–selective drugs are less likely to interfere with the secretion and regulation of insulin.

Several studies have shown that a combination of beta-blockers and thiazide diuretics, as expected, also produces an increase in the risk of developing diabetes, by approximately 20%. The National Institute for Health and Clinical Excellence in the United Kingdom, an advisory group that develops national health policy, has placed a limited caution against the combined use of beta-blockers and thiazide diuretics for people at high risk for diabetes (because of family history, impaired glucose tolerance, or obesity, for example). While the risk of diabetes-related complications for the population as a whole is relatively low, these drugs may be a source of preventable diabetes or of diminished blood glucose control in individual cases.

Of note, ACE inhibitors and calcium channel blockers have not been strongly linked to diabetes.


Nicotinic acid, or niacin, is a B vitamin commonly used to lower blood lipids (fats). It can reduce low-density lipoprotein (LDL, or “bad”) cholesterol and triglycerides and also raise high-density lipoprotein (HDL, or “good”) cholesterol. The combination of elevated LDL cholesterol and triglycerides with low HDL cholesterol is a common lipid profile in people with diabetes.

While the drug has many side effects, one of the more important ones is worsening blood glucose control. However, data on the effect of niacin on blood glucose control is not as plentiful as data on diuretics and beta-blockers. One well-controlled study of 148 people with diabetes evaluated the effects of several different doses of niacin on both blood lipids and blood glucose control. The goal of the study was to evaluate the common medical practice of avoiding prescribing niacin to people with diabetes. Fasting blood glucose levels as well as glycosylated hemoglobin (HbA1c, another measure of blood glucose control) levels were evaluated over a 16-week period. While the doses of 1,000 mg and 1,500 mg of niacin were effective for blood lipids, the higher dose resulted in an average increase in HbA1c of 0.3 percentage points, and four people on niacin left the study due to its worsening of blood glucose control. The conclusions of the study were that niacin can be safely used in people who have diabetes, but that once again, in select individuals it can have an adverse effect on blood glucose control.

In another study, niacin was tested in combination with simvastatin, another blood-lipid-lowering drug, in 160 people who had low HDL cholesterol but normal LDL cholesterol. The investigators looked mainly at the progression of lesions in coronary arteries, but they also evaluated blood glucose and insulin levels. Participants who received these two drugs demonstrated a significant reduction in coronary artery lesions and heart attacks. They also, however, had elevated insulin levels but not elevated blood glucose. This suggests that niacin may cause insulin resistance, a condition in which the body does not use insulin efficiently.

In a review article that examined trials of niacin for both cardiovascular benefits and risks pertaining to diabetes care, it was clear that niacin has significant and positive benefits for cardiovascular health (namely, reduced heart attacks) but that small increases in blood glucose and insulin levels occur that may require adjustments to diabetes therapy.

Antipsychotic drugs

Antipsychotic drugs are used to treat severe psychiatric conditions such as schizophrenia. While schizophrenia is not a common disease among people who have diabetes, among people with schizophrenia, there is a 15% prevalence of diabetes and a risk of developing it two to three times that of the general population. Some of this risk may be due to family history, poor diet, and physical inactivity. But recent evidence suggests that some drugs used to treat schizophrenia may increase the risk of developing diabetes.

A consensus statement from the American Diabetes Association and the American Psychiatric Association recognizes that antipsychotic drugs, and in particular olanzapine and clozapine, can elevate blood glucose, cause weight gain, and increase blood lipids. These drugs also raise the risk for diabetic ketoacidosis, an uncommon but extremely serious complication of diabetes. Several hypotheses have been proposed regarding how these drugs may cause diabetes, from simply inducing weight gain to impairing insulin secretion; but so far, no strong evidence explains why these drugs have this effect.

Striking a balance

There is a longer list of drugs associated with diabetes, but the evidence for each of these is not very strong, or the medicine is only used rarely. For the more commonly used drugs that are known to worsen diabetes control, it is important to note that there remains a balance between intended benefits and unwanted side effects. Glucocorticoids can stop an inflammatory process like asthma, thiazide diuretics have been shown to be very successful at reducing high blood pressure and its complications, beta-blockers do protect against heart attacks, niacin does reduce coronary artery disease, and antipsychotic medicines can make the difference between hallucinating and perceiving reality.


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