Diabetes drugs are medications prescribed to help manage diabetes mellitus, a chronic condition that affects how the body metabolizes blood sugar (glucose). These medications help people with diabetes lower their blood glucose levels.
Classification of diabetes drugs
Different classes of diabetes drugs and their modes of action
- Insulin sensitizers (Increase insulin sensitivity): Metformin, TZDs
- Insulin Secretion Stimulants (Increase insulin secretion): Sulfonylureas, Meglitinides
- Increase glucose excretion via the kidneys: SGLT-2 inhibitors
- Reduce glucose absorption from the gut: Alpha-glucosidase inhibitors
- Enhance incretin effect: DPP-4 inhibitors, GLP-1 agonists
- Other mechanisms: Bile acid sequestrants (Colesevelam) and dopamine-2 agonists act through less direct or less well-understood pathways to improve glucose control.
Insulin sensitizers - Increase insulin sensitivity
Insulin sensitizers are medications that help the body respond more effectively to insulin. They work by increasing cells' sensitivity to insulin, allowing them to take up glucose from the blood more efficiently.
Insulin sensitizers improve the ability of insulin to stimulate glucose uptake in cells, primarily in the liver, muscle, and adipose tissue. They help overcome insulin resistance that occurs in type 2 diabetes, where cells don't respond adequately to insulin's signal to absorb glucose. By improving insulin sensitivity, these medications help lower elevated blood sugar levels.
Various insulin sensitizers can work through various mechanisms, such as lowering glucose synthesis in the liver, boosting glucose uptake in peripheral tissues, or improving insulin signaling pathways.
A closer look at some of the primary insulin sensitizers is provided below:
Metformin (Class: Biguanide) - A most commonly used biguanide that primarily reduces glucose synthesis in the liver (hepatic gluconeogenesis) and increases insulin sensitivity in peripheral tissues by acting on cellular pathways that increase insulin receptor activity. It is the first line of treatment for type 2 diabetes. It’s often used alone or in combination with other medications. Side effects: Gastrointestinal issues (like nausea and diarrhea) are common but typically improve over time.
Thiazolidinediones (TZDs) - also known as glitazones- are a class of oral anti-diabetic drugs. They work by increasing the body's sensitivity to insulin. The most commonly used TZDs are pioglitazone and rosiglitazone. Its mechanism of action increases glucose uptake by muscle and fat cells and reduces glucose production by the liver. TZDs also help reduce fatty liver (steatosis) and promote fat storage in adipose tissue, which is associated with weight gain and fluid retention.
Examples: Pioglitazone (Actos), Rosiglitazone (Avandia).
Side effects: Weight gain, edema (fluid retention), increased risk of fractures, and in some cases, increased risk of heart failure (especially in patients with pre-existing heart conditions). Pioglitazone has also been linked to an increased risk of bladder cancer with long-term use.
Contraindications: TZDs are not recommended for individuals with active liver disease, heart failure, type 1 diabetes, or those already on insulin.
Monitoring: Patients taking TZDs require regular monitoring for potential side effects, including liver function tests and assessment for fluid retention.
Natural option: Certain herbs and supplements like cinnamon, fenugreek, and berberine have shown promise in enhancing insulin sensitivity.
Insulin Secretion Stimulants (Insulin Secretagogues)
Insulin secretion stimulants are compounds that enhance the release of insulin from the pancreas. Insulin is a hormone produced by the beta cells in the pancreas that helps regulate blood sugar (glucose) levels. When blood glucose level rises, such as after eating, insulin is released to facilitate the uptake of glucose into cells for energy or storage.
These drugs, known as insulin secretagogues, primarily work by targeting the ATP-sensitive potassium (K(ATP)) channels on pancreatic beta cells. By closing these channels, they stimulate insulin release.
Insulin secretagogues are primarily used in type 2 diabetes, where the body still produces some insulin. Their effectiveness depends on the presence of functional beta cells in the pancreas. Common side effects include hypoglycemia (low blood sugar) and weight gain.
Sulfonylureas - This is the oldest class of drugs used to stimulate insulin release. These drugs bind to sulfonylurea receptors on the pancreatic beta cells, which causes the cells to release more insulin. Sulfonylureas are considered insulin secretagogues. Examples: Glipizide, Glimepiride, Glyburide.
Meglitinides - They stimulate insulin secretion by binding to pancreatic beta cells. They work more rapidly and for a shorter duration than sulfonylureas. Examples: Repaglinide, Nateglinide.
Natural options: Some studies suggest that apple cider vinegar can improve insulin sensitivity and reduce postprandial blood sugar spikes. Herbs like Gymnema Sylvestre, fenugreek, and bitter melon are known for their potential to boost insulin production.
Glucose Excretion Promoters - Glucose reabsorption inhibitors
Glucose excretion promoters are substances that enhance the process of glucose excretion in the urine. Finally, they can be related to renal processes, where the kidneys filter glucose from the blood and excrete it in the urine. These agents are often used in the management of type 2 diabetes, especially in cases where other treatments aren't sufficient to control blood sugar.
Here is the main type of glucose excretion promoter:
SGLT2 Inhibitors (Sodium-Glucose Cotransporter-2 Inhibitors) - SGLT2 is a protein found in the kidneys that helps reabsorb glucose from the urine back into the blood. When SGLT2 inhibitors block this protein, preventing glucose from being reabsorbed into the bloodstream. As a result, excess glucose is excreted through the urine.
Examples: Canagliflozin (Invokana), Dapagliflozin (Farxiga), Empagliflozin (Jardiance), and Ertugliflozin (Steglatro).
Side effects: Increased risk of urinary tract infections (UTIs), Genital yeast infections, Dehydration (due to increased urine output), increased urination, rarely, diabetic ketoacidosis (DKA), especially in patients with type 1 diabetes.
Additional benefits: Weight loss (due to glucose loss in the urine) and Lower blood pressure (a mild diuretic effect).
Carbohydrate Absorption Reducers - Starch blockers
Carbohydrate absorption reducers, also known as carb blockers, are substances that limit the digestion and absorption of carbohydrates, particularly starches. They work by inhibiting enzymes that break down complex carbohydrates into sugars, or by delaying the digestion process. This can potentially lead to a decreased amount of glucose absorbed after eating, thus helping lower post-meal blood sugar spikes (known as postprandial hyperglycemia).
Here’s an overview of the main types of carbohydrate absorption reducers: Alpha-Glucosidase Inhibitors - These drugs inhibit alpha-glucosidase enzymes in the small intestine, which are responsible for breaking down complex carbohydrates (such as starches) into simple sugars (like glucose). By inhibiting these enzymes, alpha-glucosidase inhibitors delay the digestion and absorption of carbohydrates, meaning glucose enters the bloodstream more slowly and gradually.
Examples: Acarbose (Precose) and Miglitol (Glyset). Effect: Reduces postprandial blood glucose spikes by slowing down carbohydrate absorption. Side effects: Gastrointestinal issues are common, including bloating, flatulence (gas), diarrhea, and abdominal pain, since undigested carbohydrates ferment in the gut. Use: Often used as an adjunct treatment to other diabetes medications, particularly for managing after-meal blood glucose levels.
Natural drug-free options: White kidney bean extract and dietary fibers. White kidney bean extract is a popular natural option, often found in weight management supplements.
Dietary Fiber (Natural Carb Absorption Reducers) - While not a "drug," dietary fiber (particularly soluble fiber) can help reduce the absorption of carbohydrates. Fiber forms a gel-like substance in the gut, slowing the digestion and absorption of nutrients, including carbohydrates. This results in a slower rise in blood sugar after meals, which can be beneficial for people with diabetes.
Examples: Foods high in soluble fiber include oats, beans, lentils, flaxseeds, and certain fruits and vegetables (like apples and carrots). Effect: Reduces postprandial blood glucose spikes by slowing the absorption of carbohydrates. Side effects: Can cause bloating, gas, and abdominal discomfort, especially if fiber intake is suddenly increased.
Incretin-Based therapies
Incretins are natural hormones released in response to food intake that help manage blood glucose by enhancing insulin secretion, inhibiting glucagon (a hormone that raises blood sugar), and slowing gastric emptying.
Incretin-based therapies are a class of medications that work by enhancing the effects of natural incretin hormones, which stimulate insulin release and suppress glucagon secretion in response to food intake. These therapies are effective at lowering blood glucose levels and can also lead to weight loss. The Two Main Types of Incretin-Based Therapies: GLP-1 Receptor Agonists (Glucagon-like peptide-1) and DPP-4 Inhibitors (Dipeptidyl peptidase-4 inhibitors).
GLP-1 Receptor Agonists - GLP-1 receptor agonists are synthetic versions of the incretin hormone. They bind to GLP-1 receptors on pancreatic beta cells to stimulate insulin release and reduce glucose production by the liver.
Additionally, they also act on the brain to promote satiety (feeling of fullness), which can help with weight loss—a key benefit for many with type 2 diabetes. Examples: Exenatide (Byetta, Bydureon), Liraglutide (Victoza, Saxenda), Semaglutide (Ozempic, Wegovy), Dulaglutide (Trulicity), and Lixisenatide (Adlyxin). Side effects: Gastrointestinal issues like nausea, vomiting, diarrhea, and constipation (especially when starting treatment). Risk of pancreatitis (in rare cases); Risk of thyroid tumors (especially in rodents, but not conclusively proven in humans).
DPP-4 Inhibitors - DPP-4 inhibitors don't increase insulin secretion as much as GLP-1 agonists, but they still enhance the body's natural incretin response. The primary role of DPP-4 inhibitors is to help regulate glucose by promoting insulin secretion and suppressing glucagon secretion, especially after meals.
Examples: Sitagliptin (Januvia), Saxagliptin (Onglyza), Linagliptin (Tradjenta), and Alogliptin (Nesina). Side effects: Headache and upper respiratory infections, Risk of pancreatitis (although much lower compared to GLP-1 agonists), Risk of joint pain or muscle pain. In rare cases, skin reactions and allergic reactions can occur.
GLP-1 Agonists are generally more effective at lowering HbA1c (a long-term marker of blood sugar control) and often result in weight loss, making them a preferred choice for people with obesity and type 2 diabetes.
DPP-4 Inhibitors, while effective, tend to have milder effects on blood sugar and are generally used when weight loss is not a primary concern or when tolerability is a key factor (since they usually have fewer gastrointestinal side effects than GLP-1 receptor agonists).
Other diabetes drugs
Bile Acid Sequestrants - Bile acid sequestrants are a class of medications used to lower LDL (bad) cholesterol by binding to bile acids in the intestines, preventing their reabsorption and their elimination in the stool. The body needs to produce more bile acids from cholesterol in the liver to compensate for the losses, which reduces the amount of cholesterol in the blood circulation.
The mechanism that reduces cholesterol may also improve insulin sensitivity and lower blood sugar in some people with type 2 diabetes, though the effect is mild compared to other diabetes medications.
Here’s an overview of how bile acid sequestrants work, their effects, and their use in type 2 diabetes:
Examples of Bile Acid Sequestrants: Cholestyramine (Questran), Colestipol (Colestid), and Colesevelam (Welchol).
Colesevelam (Welchol) has been shown to help lower HbA1c by about 0.5–1% in people with type 2 diabetes. Improved insulin sensitivity, Reduced liver glucose production, and Changes in bile acid metabolism that might indirectly improve glucose homeostasis.
Side Effects: Constipation is the most common side effect, which can often be managed with adequate fluid intake and fiber. Bloating, indigestion, and gas are also reported. Malabsorption of fat-soluble vitamins (such as vitamins A, D, E, and K) can occur with long-term use because bile acids are important for the absorption of these vitamins.
Drug Interactions: Bile acid sequestrants can interfere with the absorption of certain medications, including statins, warfarin, digoxin, and others. It’s important to take these medications separately (usually 1–4 hours apart).
Dopamine D2 agonists - Dopamine D2 agonists are a class of medications that activate dopamine D2 receptors in the brain, mimicking the effects of dopamine and are used to treat various conditions, including Parkinson's disease, hyperprolactinemia, and type 2 diabetes. These agonists can be categorized into ergoline and non-ergoline types, with examples like bromocriptine and cabergoline being ergoline, and pramipexole and ropinirole being non-ergoline. Bromocriptine, a D2 agonist, has been approved for managing hyperglycemia in type 2 diabetes, though its exact mechanism is still under investigation.
Dopamine agonists can cause side effects, including nausea, dizziness, sleep disturbances, and compulsive behaviors. Careful monitoring and dose adjustments are necessary when using dopamine agonists, especially in individuals with pre-existing conditions.
Diet, exercise and weight reduction should be the cornerstone of diabetes management.
You can manage your diabetes by losing some weight, increasing physical activity (or regular exercise), and following a proper diet. Losing 10 or 15 pounds or 4.5 to 6.8 Kg can sometimes help you reach your target. Always check with your doctor before you stop taking your diabetes pills or start your treatment by lifestyle change alone (without medication).