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• Posted July 5, 2023

Diabetes Medications: Choosing Which Ones Are Best for You

You have been diagnosed with type 2 diabetes. What are your medication options?

That depends on what type of diabetes you have and what risk factors you carry.

In type 2 diabetes, the body becomes resistant to the insulin and the pancreas has to make more. Insulin resistance can be caused by obesity, lack of exercise, medication, stress or hereditary factors. Initially, the pancreas will make more insulin to compensate, but eventually the pancreas will tire and not be able to make enough insulin. Diet, exercise, weight loss and medication can help you manage your glucose.

Let's focus on the medications that can help manage type 2 diabetes.

Symptoms of diabetes include excessive urination, excessive thirst, urinary tract infection, genital yeast infections, weight loss, blurry vision and fatigue. But the most common symptom of diabetes or high glucose is no symptoms at all.

That's why it is important, particularly if you have risk factors, to be screened for diabetes. Risk factors include obesity, family history, personal history of gestational diabetes, use of steroid or HIV medications, fatty liver disease, prediabetes, polycystic ovarian syndrome (PCOS), or high triglycerides (a type of blood fat).

With 12 classes of diabetes medications, each with its own mechanism of action and many with nearly impossible names to pronounce, there's no wonder patients may be confused about which diabetes medication is right for them.

The American Diabetes Association (ADA) recommends that the decision on which medications to use be between the patient and his or her doctor, taking into account factors like cost, other beneficial effects on heart and kidney disease, long-term risk of hyperglycemia (high blood sugar), including life expectancy and desire for pregnancy, and risk of hypoglycemia (low blood sugar).

Do you have a compelling indication for one of these newer diabetes medications?

For patients with heart or kidney disease, some of the newer medications, known as GLP-1 agonists and SGLT2 inhibitors, have been shown to reduce heart attack, stroke, admission for heart failure, progression of kidney disease and development of needing dialysis. The ADA states that for patients who have blockages in the heart arteries, history of heart attack or heart failure, chronic kidney disease, or large amounts of protein called albumin in their urine, these are compelling indications to take GLP-1 agonists or SGLT2 inhibitors. SGLT2 inhibitors are preferred for patients with albumin-creatinine ratio (uACR) levels over 200 mg/g and for patients with a history of heart failure.

If cost is an issue, metformin, sulfonylureas and thiazolidinediones are all generic. Metformin is typically the first medication doctors such as myself and others in Duke University's Endocrinology, Metabolism and Nutrition Division turn to.

It's important to understand that many patients with type 2 diabetes are insulin-deficient or at least unable to produce as much insulin as they need. For that reason, if glucose is high and not responding to other medications and diet, insulin should be started. For patients with infection or non-healing wounds or weight loss, insulin is often the best medication to choose. Patients with a history of pancreatic insufficiency -- pancreatitis, hemochromatosis, cystic fibrosis -- may require insulin. Patients with type 1 diabetes absolutely need insulin as the pancreas is not producing insulin because of autoimmune destruction of the pancreas.

However, even if the benefits of these medications seem something a patient would like to contemplate, side effects and contraindications of these medications should also be considered.

Diabetes medication classes

Metformin

Metformin helps the liver recognize insulin and reduces glucose. This medication can cause gas and diarrhea. It should not be used if there is stage 4 or 5 chronic kidney disease. The side effects abate with time if patients take the medications daily. Stopping and starting the medication or eating high-carbohydrate food can worsen the side effects. And while they don't cause kidney disease, if kidneys start to fail, metformin should be used with caution and sometimes discontinued.

Sulfonylureas

Sulfonylurea medications increase pancreatic insulin secretion. This class of medications can cause hypoglycemia (low blood sugar). For elderly patients, it's best to manage diabetes without this class of medications, if possible, as it is often associated with serious hypoglycemia. Because the medication is not very expensive, it is often an agent of choice for those looking to reduce costs. However, if hypoglycemia events become common, the drugs should be discontinued.

SGLT2 inhibitors

SGLT2 inhibitors work by taking glucose in the blood and putting it in the urine.

SGLT2 inhibitors can increase the risk of urinary tract infections and skin infections around the genital areas that if left untreated can result in a dangerous and potentially deadly infection called Fournier's gangrene. SGLT2 inhibitors also drain calcium from the body and can worsen osteoporosis. Patients with very normal blood pressure should be cautioned to keep well-hydrated and if on blood pressure medication, doses should be lowered.

GLP-1 agonists

GLP-1 agonists increase insulin secretion when appropriate. They also slow gastric emptying, causing a feeling of fullness. Slower gastric emptying also reduces rapid carbohydrate digestion, lowering the chances of a glucose spike. GLP-1 agonists also increase satiety. Most GLP-1 agonists are injectable, but one comes in a pill (Rybelsus). Of note, agonists is a fancy medical word that means “acts like.” GLP-1 is a natural hormone secreted by the intestines. It's called an incretin hormone because it is secreted by the intestines.

GLP-1 agonist medications can cause nausea and vomiting, but they have also been associated with pancreatitis and pancreatic cancer. Whether GLP-1 agonists cause pancreatic cancer or pancreatitis is up for debate, but doctors don't advise this class of medications in patients who have a history or who are at risk for pancreatic cancer or pancreatitis. Risks for pancreatitis include high triglycerides and/or gallstones. DPP-IV inhibitors do not cause nausea and vomiting, but are not as strong as GLP-1 agonists. They also are linked to increased risk of pancreatic cancer and pancreatitis. Both GLP-1 and DPP-IV are associated with increased incidence of medullary thyroid cancer in rodents. This association has not been borne out in human studies or use but doctors do not recommend it in patients with history or family history of medullary thyroid cancer or multiple endocrine neoplasia.

Dual GIP/GLP-1 agonists

Tirzepatide (Mounjaro) has the same action as GLP-1 agonists but also acts like a gastric intestinal peptide (GIP). GIP increases glucagon production. Glucagon increases glucose. Why would you want a diabetes medication to increase glucose? Isn't the point to decrease glucose? Glucagon is there when glucose goes too low. This combination medication works to lower glucose to normal, but not too low, levels. It also causes more weight loss than GLP-1 agonists alone.

Thiazolidinediones

Thiazolidinedione medications (common names are pioglitazone or rosiglitazone) improve insulin resistance and recruit cells to become fat cells to take in extra glucose. These drugs lower glucose well. However, this class of medications can cause weight gain, and volume overload leading to heart failure and swelling.

DPP-IV inhibitors

DPP-IV inhibitors slow the breakdown of natural GLP-1. Thus, they boosts the life span of natural GLP-1. DPP-IV inhibitors do not cause nausea and vomiting, but are not as strong as GLP-1 agonists. They also are linked to increased risk of pancreatic cancer and pancreatitis. Both GLP-1 and DPP-IV drugs are associated with increased incidence of medullary thyroid cancer in rodents.

There are a lot of options for the medical treatment of type 2 diabetes. Along with exercise and a healthy diet, you can find a regimen that works for you to help you maintain or improve glucose control.