Type 2 diabetes can occur for two reasons. The first is that your body no longer responds well to insulin. The second is that your pancreas cannot make enough insulin to manage your blood sugar. As a result, sugar cannot get into your cells to give your body energy. That causes sugar levels to rise in your bloodstream. When sugar levels are high for too long, it can cause problems like impaired vision, kidney injury, or heart disease. Lifestyle changes and meds can work together to keep blood sugar in range and prevent these problems from developing. Oral diabetes meds work by targeting the following four things:
- Helping the body to respond better to the insulin it’s producing
- Helping the pancreas to release more insulin
- Reducing the body’s glucose (sugar) production
- Getting rid of extra blood sugar through the kidneys (urinating it out)
It’s not uncommon to be on multiple meds to manage diabetes. Often doctors start people on one medication, then add other. The number of meds you are on does not reflect how well you manage your diabetes. Since diabetes changes over time, it’s normal to need your meds to change, too.
Oral Medications:
Metformin (Glucophage, Glucometza):
Metformin is typically the first medication prescribed when a person is diagnosed with diabetes or prediabetes.
Class: Biguanides
How does it work?
It lowers the amount of glucose (sugar) released by the liver. This is especially true in times of fasting (like overnight) or if meals are skipped. It also helps the body respond better to the insulin it’s already making.
Benefits:
Metformin helps lower cholesterol, encourages weight loss, does not cause low blood sugar, and is low cost. It has been shown to lower A1c 1.0-2.0%. Metformin has been used for many years and has been shown to be safe when taken over long periods of time.
Side effects: Gastrointestinal distress: Diarrhea, nausea.
Typical dose: 500-1000 mg once or twice daily. Depending on the formulation, it is usually taken with food.
Pro tip: Take metformin with food to reduce stomach distress. These symptoms typically stop after a few weeks on the medication. If you experience side effects, talk to your doctor about the extended release (ER or XR) version where the side effects are minimized. Some doctors will also start with a lower dose and gradually increase to reduce side effects.
Glyburide (DiaBeta), Gliclazide (Diamicron), Glimepiride (Amaryl):
Class: Sulfonylureas
How do they work?
These medications help the pancreas release more insulin to lower blood sugar levels.
Benefits: Lowers A1c 1.0-2.0%
Side effects:
Low blood sugar (hypoglycemia).
Possible weight gain related to the increased insulin release. Insulin causes the body to store extra energy as fat.
Pro tip: Since these meds lower blood sugar levels, it’s important to take them right before eating to prevent low blood sugar. If you are sick, skipping meals, or unable to eat, contact your doctor for possible dosing changes to avoid hypoglycemia (low blood sugar).
In some people, these meds work well at first but stop working later on. The pancreas may not be able to produce as much insulin as it once did, making the medication less effective.
Typical dose:
Glyburide (DiaBeta): 2.5-20 mg
Gliclazide (DIamicron): 80-320 mg
Glimepiride (Amaryl): 1.0-8.0 mg
Sitagliptin (Januvia), Saxagliptin (Onglyza), Linagliptin (Tradjenta)
Class: DPP-4 inhibitors
How do they work?
These meds work to lower blood sugar in two ways. First, they increase the insulin the body releases after eating. Second, they help decrease the amount of glucose (sugar) released by the liver.
Benefits: They do not cause weight gain or low blood sugar levels. Can lower A1c 0.6-0.8%.
Side effects:
Headache, runny nose, and stomach distress, like diarrhea or abdominal pain. Side effects are rare, although they can occur. If you notice any unusual symptoms, notify your healthcare provider.
Onglyza (Saxagliptin) can increase the risk of heart failure. If you experience shortness of breath, weakness, or swelling, notify your doctor.
Pro tip:
These meds increase the production of insulin after meals. Check your blood sugar before and 2 hours after to make sure they are working properly.
Typical dose:
Taken once daily with or without food.
Sitagliptin (Januvia): 100 mg once daily (the dose can be reduced to 25-50 mg daily if kidney function is reduced)
Saxagliptin (Onglyza): 5 mg once daily (the dose can be reduced to 2.5 mg daily if kidney function is reduced)
Linagliptin (Tradjenta): 5 mg once daily (no dose adjustment needed for people with kidney or liver disease)
Pioglitazone (Actos)
This is part of the class called: Thiazolidinediones or TZDs
How do TZDs work?
These meds help your body better use the insulin it is making.
Benefits: It can lower A1c by 0.5-1.0%.
Side effects:
Weight gain, likely due to extra fluid, may occur. If you gain 7 or more pounds (3.3 kilograms), notify your doctor. You should also tell your doctor if you notice swelling of the legs or feet or have shortness of breath, trouble breathing at night, or an unexplained cough.
Typical dose:
They can be prescribed once or twice daily.
Pioglitazone: 15-45 mg daily
Rosiglitazone: 2-8 mg daily
Pro tip: It can take 8-12 weeks to see the full impact of these meds. Don’t be discouraged if you don’t see an immediate improvement.
Canagliflozin (Invokana), Dapagliflozin (Forxiga), Empagliflozin (Jardiance)
Class: SGLT2 inhibitors
How do they work?
These meds help your body to remove extra glucose (sugar) through the urine. This helps to lower blood sugar.
Benefits: Lower A1c 0.5-0.7%, weight loss of 4-6 lbs
Side effects:
The rate of urinary tract infections (UTIs) is increased by a small amount. They also increase the risk of genital fungal infections like vaginal yeast infection, which can happen in up to 10% of people who take the medication.
Increased urination.
Increased risk for diabetic ketoacidosis. Especially with stressors like surgery or an extremely low carb diet, diabetic ketoacidosis can occur even if blood sugars are normal.
Dehydration can occur in those who have low blood pressure or kidney disease, especially in those over 65 years of age.
Typical dose:
Canagliflozin (Invokana): 100-300 mg daily
Dapagliflozin (Farxiga): 10 mg daily
Empagliflozin (Jardiance): 10-25 mg daily
Pro tip: These meds can cause more frequent bathroom breaks (urination). Try not to take them before bed or during daytime activities; it’s best to take before your first meal of the day. If you have low blood pressure or are 65 or older, be sure to drink plenty of water.
Injectables:
Liraglutide (Victoza), Terzapatide (Mounjaro), Dulaglutide (Trulicity), Semaglutide (Ozempic) (Rybelsus oral tablet),
Class: GLP-1 Receptor Agonists (GLP-1 RA)
How do they work?
These injectable meds help lower blood sugar levels after meals by:
- Helping your brain feel like your appetite is satisfied.
- Helping your pancreas release insulin after eating.
- Slowing down the digestion of food in the stomach so you feel fuller after meals.
- Lowering the amount of glucose (sugar) released by the liver.
Benefits: Weight loss is common with this class of meds. It is recommended for people with a BMI of 30 or above or for someone with a BMI of 27 who has diabetes, high blood pressure, or both. This medication alone does not cause low blood sugar levels. Some meds in this class (Victoza and Ozempic) can reduce the risk of heart disease.
Some of these medications (such as Trulicity, Victoza, and Ozempic) can also reduce heart disease.
Side effects:
Nausea is the most common side effect. It usually decreases with time. To lower this risk, eat slowly, and stop when you start to feel full.
Other side effects include: Vomiting, weight loss, and injection site reaction. If severe abdominal pain and vomiting occur, stop the medication. Report these symptoms to your doctor.
There is a thyroid C-cell tumor warning for liraglutide (Victoza) and dulaglutide (Trulicity). Avoid these if there is a family history of medullary thyroid cancer. Notify your doctor if there is hoarseness or a feeling of a lump in the throat.
Typical dose:
Liraglutide (Victoza): Starting dose is 0.6 mg daily for 1 week, then is increased to 1.2 mg daily This medication can be increased to 1.8 mg once daily
Tirzepatide (Mounjaro): Starting dose is 2.5 mg once per week and can be increased to 5-15 ever week at 4-week intervals.
Dulaglutide (Trulicity): Starting dose is 0.75 mg once per week and can be increased to 1.5 mg once weekly. Further increases to 3 mg and 4.5 mg once weekly are also possible
Semaglutide (Ozempic – an injectable): starting dose is 0.25 mg weekly for 4 weeks, then is increased to 0.5 weekly. Can increase to 1.0 mg weekly
Semaglutide (Rybelsus – an oral tablet): 3 mg pill daily for 4 weeks, then is increased to 7 mg daily. Can increase to 14 mg daily if needed. Take on an empty stomach with water
Pro tips:
- Since this class of medications slows down the emptying of your stomach, other medications, like birth control pills, pain pills, and antibiotics, may be impacted. It’s recommended to take pain pills 2 hours before your injection and other medications 1 hour before your injection.
- Some of these medications come in a combined form with long-acting insulin. So, if you are also taking a long-acting insulin, you may want to discuss the option of switching to a combined GLP-1 RA + long-acting insulin to reduce the amount of total injections you’re taking. These medications are called: Soliqua (iGlarLixi), Xultophy (iDegLira).