Steroid drugs can induce a form of iatrogenic Cushing’s syndrome, and are probably the most widely used drugs which confer a high risk of diabetes.
Corticosteroids mimic the action of cortisol, so are responsible for bringing on our body’s classic stress response of higher blood pressure and increased blood glucose levels. Corticosteroids blunt the action of insulin and promote hepatic gluconeogenesis, possibly by activation of liver x receptor-β involving phosphoenolpyruvate carbosykinase gene transcription.
Glucocorticoids also block the entry of glucose into the muscles and fat tissue by preventing glucose-transport proteins in the cells of those tissues from reaching the cell membrane, where they normally serve to remove glucose from the blood. These drugs have many other serious side effects, including osteoporosis, suppression of the adrenal glands, and cataracts.
The mechanism responsible for glucose intolerance after corticosteroids administration is similar to that of type 2 Diabetes since steroids increase insulin resistance, which can be up to 60%-80% depending on the dose and type used. So, Steroids are the main cause of drug-induced hyperglycemia. They not only exacerbate hyperglycemia in patients with known diabetes mellitus (DM), but also cause DM in patients without documented hyperglycemia before the initiation of glucocorticoids (GC) therapy, with an incidence that can reach up to 46% of patients, and increases in glucose levels up to 68% compared to baseline.
Hyperglycemia occurs in a majority of hospitalized patients receiving high doses of corticosteroids. Furthermore, in some populations they can precipitate acute complications such as nonketotic hyperosmolar state, and diabetic ketoacidosis and in a few instances death, especially in patients with pre-existing DM.
So, the risk of ketoacidosis as well as hyperglycemia should be considered in the course of glucocorticoid therapy.
Observational studies suggest that systemic absorption of topical steroids could be diabetogenic.
Birth control pills
Use of oral contraceptives containing estrogen is significantly associated with higher fasting insulin and insulin resistance. Past use of oral contraceptives increases the prevalence of insulin resistance and diabetes among postmenopausal women. Diabetes Risk Almost 35% Higher if Pill Used for >6 Months.
So, when it comes to oral contraception for diabetic women, experts most frequently recommend combination birth control pills that contain lowest dose of estrogen possible and norgestimate.
The exact mechanism of how thiazide diuretics (Hydrochlorothiazide and chlorthalidone) cause the development of hyperglycemia is unknown. However, it is postulated to involve worsening of insulin resistance, inhibition of glucose uptake, and decreased insulin release, among other pathways. In addition, thiazide diuretics are postulated to down-regulate peroxisome proliferator-activated receptor gamma, thereby decreasing insulin release in addition to activating the reninangiotensin-aldosterone system, thus resulting in elevated levels of aldosterone and resulting hyperglycemia.
Another proposed mechanism of thiazide-induced hyperglycemia involves thiazide-induced hypokalemia possibly through impairment of potassium-dependent insulin release in response to glucose load. However, hypokalemia is an inconsistent finding in people who develop hyperglycemia or diabetes when taking a thiazide diuretic.
In studies, those taking HCTZ had fasting blood sugar levels that were 2-3 mg/dl higher than those not taking the drug, and as a result, also had a 12% to 18% higher risk for diabetes. Hydrochlorothiazide has been implicated in contributing to new-onset diabetes in as few as 9–18 weeks of therapy initiation.
Beta-blockers work by blocking the release of adrenaline and noradrenaline which helps to reduce blood pressure and reduce heart rate. Diabetes-unfriendly beta-blockers (Atenolol, Bisoprolol and Metoprolol) effectively treat high blood pressure but may raise blood sugars as well. β-blockers are thought to contribute to the development of hyperglycemia by impairing the release of insulin from the pancreatic β-cell.
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. Interestingly, carvedilol and nebivolol are not associated with the development of hyperglycemia or new-onset diabetes.
Diabetes-friendly beta-blockers like carvedilol, nebivolol, and labetalol are associated with fewer hospitalizations for hyperglycemia but increased all-cause rehospitalizations among nursing home residents with diabetes and recent acute myocardial infarction, according to research published in Diabetes, Obesity & Metabolism.
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%. Development of adverse metabolic effect, including new-onset diabetes mellitus associated with short-term exposure to hydrochlorothiazide and atenolol was more common in those with abdominal obesity.
ACE inhibitors and calcium channel blockers have not been strongly linked to diabetes. ACE inhibitors and calcium channel blockers have not been strongly linked to diabetes.
Drugs that treat anxiety, ADHD, depression, and other mental health problems.
Atypical antipsychotics (aripiprazole, risperidone, olanzapine, quetiapine, ziprasidone, clozapine, lanzapine/fluoxetine) are associated with hyperglycemia and an increased risk of new-onset diabetes.
A cohort of French women currently taking any antidepressant medication were more likely to develop type 2 diabetes during 6 years of follow-up compared with nonusers, independent of severe depressive symptoms. The use of antidepressants was associated with a 34% increased risk for developing type 2 diabetes (HR = 1.34; 95% CI, 1.12-1.61) compared with nonusers.
The schizophrenia and depression medications, clozapine, olanzapine and quetiapine have been linked to a three-fold increase in diabetes risk. CLozapine and olanzapine, can cause much worse metabolic side-effects including body weight gain, obesity, hyperlipidaemia, insulin resistance, hyperglycaemia and diabetes (Foley and Morley, 2011; De Hert et al., 2012; Deng, 2013; Lipscombe et al., 2014; Stubbs et al., 2015).
The development of diabetes and resultant hyperglycemia, however, is likely a complex interplay of the atypical antipsychotic’s likelihood of promoting weight gain (e.g., olanzapine and clozapine) through the involvement of multiple mechanisms. These mechanisms involve, but are not limited to, antagonism at 5-HT receptors (serotonin receptors) mainly involving 5-HT2C, which is involved in regulation of food intake; antagonism at central histamine H1 receptors; development of insulin resistance through effects on cellular glucose transporters; compromised insulin secretion; and alterations in leptin levels.
Although weight gain occurs with conventional antipsychotic agents such as haloperidol, greater weight gain definitely occurs with chlorpromazine, olanzapine, and clozapine and may occur with risperidone and quetiapine. 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.
Phenytoin (Dilantin) and valproic acid (Depakene) are seizure medications that may block the pancreas from releasing insulin and cause blood sugar levels to rise. In a study of patients with epilepsy, almost half of the patients treated with valproic acid were found to have high blood sugar levels.
Long-term use of the following antidepressant medications is associated with an increased risk for diabetes: fluvoxamine (Luvox), mirtazapine (Remeron), paroxetine (Paxil) and sertraline (Zoloft). More specifically, an increased risk for high blood sugar is seen with high or moderately high daily doses of these drugs (not low daily doses).
Fluoroquinolones (Gatifloxacin, levofloxacin and ciprofloxacin) are the only class of antibiotics that can elevate blood sugar, especially in older adults or folks who are already diabetic. The risk for high blood sugar with these medications is relatively low. However, gatifloxacin is more likely to cause high blood sugar than levofloxacin or ciprofloxacin. Interestingly, gatifloxacin is also associated with the development of hypoglycemia. The proposed hypoglycemic mechanism involves binding of the antibiotic to the pancreatic β-cell similar to the action of sulfonylureas.
Calcineurin Inhibitors (CNIs)
Calcineurin is a protein phosphatase that activates T cells of the immune system. The CNIs cyclosporine, sirolimus, and tarcrolimus are often used to avoid allograft rejection in transplantation therapy.
The postulated mechanism of hyperglycemia results from inhibition of pancreatic islet β-cell expansion promoted by calcineurin.
Prostate Drugs Increase Diabetes Risk
The risk of developing new onset type 2 diabetes appears to be higher in men with benign prostatic hyperplasia exposed to 5α-reductase inhibitors than in men receiving tamsulosin, but did not differ between men receiving dutasteride and those receiving finasteride. Men being treated with dutasteride or finasteride for benign prostatic hyperplasia (BPH) have a roughly 30 per cent increased risk of developing diabetes.
Researchers have discovered a link between SGLT2 inhibitors and Fournier gangrene – an infection that affects the genitals.
Leuprolide and Goserelin are common medications used to treat prostate cancer. Using either of them can increase your risk for diabetes by almost 30%. How? Both drugs cause your body to be more resistant to the sugar-lowering effects of insulin.
Statins May Double the Risk of Type 2 Diabetes
The findings, which appear in the journal Diabetes Metabolism Research and Reviews, revealed that people who took statins were more than twice as likely to receive a diabetes diagnosis than those who did not take the medication. Additionally, people who took statins for longer than 2 years were more than three times as likely to develop diabetes.
Individuals who take cholesterol-lowering statins may be at higher risk for developing high blood sugar levels, insulin resistance, and eventually type 2 diabetes, according to an analysis published in the British Journal of Clinical Pharmacology. Compared with participants who never used statins, those who used statins tended to have higher concentrations of serum fasting insulin and insulin resistance. Participants who ever used statins had a 38 percent higher risk of developing type 2 diabetes during the study.
Regular use of statins, a group of drugs used to treat high cholesterol, can cause as much as a 12% increase in blood sugar levels. How? Insulin is the hormone that helps your cells take up glucose. Statin medications result in less insulin secretion and make your cells less sensitive to insulin. More potent statins like atorvastatin, rosuvastatin and simvastatin cause a larger increase in blood sugar than less potent statins like pravastatin.
Protease inhibitors are essential components of antiretroviral therapy for the treatment of people with HIV and AIDS. Protease inhibitor–associated hyperglycemia may occur in treated people with or without diabetes and occurs in 3–17% early in therapy or after extensive and prolonged use.
Hyperlipidemia and insulin resistance are induced by protease inhibitors independent of changes in body composition in patients with HIV infection. Ritonavir has been shown to directly inhibit glucose transporter type 4 activity in vivo, accounting for its ability to cause hyperglycemia.