How to Handle Non-Insulin Medication Side Effects

Diabetes care has come a long way since insulin was discovered back in the 1920s (shout out Dr. Frederick Banting and Dr. Charles Best!). Today, there are many non-insulin therapies that can help work to lower one’s blood sugar and reduce risk of complications from diabetes (you know, the fun stuff like heart attack, strokes, kidney disease), yet, side effect management can be challenging to navigate. Considering diabetes management is not a “one size fits all” approach, some of these options may work well for some people while not for others.

We’re going to highlight the most common side effects to expect, which medications are associated with the specific side effect, and considerations to best manage these side effects. 

Upset stomach

AKA diarrhea, constipation, nausea, vomiting, stomach fullness

Medications with this side effect

• Metformin (Glucophage©; pill)
• Tirzepatide (Mounjaro©; injection)
• Dulaglutide (Trulicity©; injection)
• Liraglutide (Victoza©; injection)
• Semaglutide (Ozempic©; injection)
• Semaglutide (Rybelsus©; pill)

Why + when does this happen? 

These medications directly impact your gut and brain which lead to change how you feel after you eat. Diarrhea, constipation, nausea, and vomiting are common with all medications listed, while stomach fullness most associated with all of the above meds except Metformin. Expect to notice some degree of upset stomach when you start medication and if you increase the dose. 

What can I do?

Management (if mild) will depend on the exact symptom! Here are some different strategies that you can try, but be sure to always talk through strategies with your provider. 

1. Over the counter medications can be helpful, so ask your provider if you would be a good candidate for:

• Diarrhea = loperamide (Imodium©)
• Constipation = polyethylene glycol 3305 (Miralax©), docusate sodium and sennosides (Colace© 2-in-1)
• Nausea = bismuth subsalicylate (Pepto-Bismol©; fun fact this can turn your tongue or stool black – this is temporary and harmless!)

 2. Medication timing

• If taking Metformin, take each dose after a meal.
• Take first dose of your non-insulin medication on a lowkey day when you do not have any mandatory obligations planned (example: work, first date, family gathering, workout class).
• Increase dose slowly (discuss with your provider!)
  • Be extra cautious if you also have a gastric condition at baseline (ex: Crohn’s disease, Irritable Bowel Syndrome, etc). For example, instead of increasing once a week ask your provider if you could instead try once a month. Or instead of increasing once a month ask your provider if you could instead try once every 3 months

3. Eat balanced meals (yes, even when you’re feeling full — prioritize protein, fiber, and carbs!)

GLP-1 medications like tirzepatide (Mounjaro©), dulaglutide (Trulicity©), liraglutide (Victoza©), and semaglutide (Ozempic© or Rybelsus©) can make you feel full faster — and that can make it tempting to skip parts of your meal, especially heavier foods like protein or carbs. But your body still needs all three macronutrients (protein, carbohydrates, fat)  to function well.

Try to structure your plate with:

• A palm-sized serving of protein (meat, fish, eggs, tofu, etc.) to maintain muscle and keep you feeling satisfied without blood sugar crashes later
• Half your plate of fiber-rich veggies to support digestion and gut health.
• A quarter of your plate of carbohydrates to provide energy and fuel your brain! Choose complex carbs when you can (like whole grains, beans, sweet potatoes, or fruit).

If you find yourself getting full quickly, try eating slowly, tuning into your body’s cues, or breaking meals into smaller portions throughout the day. The goal isn’t to eat less — it’s to eat balanced so your body gets what it needs, even on a smaller appetite.

4. Some foods/drinks can increase indigestion– consume strategically! 

• Things like alcohol, fried food, and carbonated beverages can increase risk of indigestion (Ozempic© burps are real y’all!). 
• Smart swaps
  • Juice/sweetened beverages: swap with sugar free juice (many restaurants serve mocktails you could request be made sugar free too!)
  • Ice cream: swap with greek yogurt ice cream (Yasso brand bars slap!)
  • Chips: swap with pork rinds, cheese crisps, roasted pepperoni chips, roasted veggie chips, flaxseed crackers, almond flour crackers, popcorn, nuts, beef jerky
  • White bread/pasta/rice: swap with wheat bread/pasta/rice. Some brands I have found that are tasty are Dave’s Killer bread, Joseph’s Lavash bread, Banza pasta, Barilla protein pasta
  • Other tips/tricks:
    1. Cooking pasta/rice in bone broth can add more protein 
    2. Eating carbs cold rather than hot may have a smaller spike on your blood sugar. Instead of mac and cheese for lunch, try out a pasta salad (bonus if you add in veggies!)

• Time food choices with your meds. Remember, there are no “bad” foods/drinks, as long as you practice consuming them in moderation. So go drink that glass of champagne at your cousin’s wedding! Eat the giant hotdog at the baseball game! Instead of cutting them out, try to change your mindset to how you can get the most bang for your buck (after all these meds aren’t cheap). Timing is key. Schedule consuming alcohol, fried food, or carbonated beverages days 5-7 after the day you take injection if you are taking a weekly injectable medication such as (tirzepatide (Mounjaro©), dulaglutide (Trulicity©), or semaglutide (Ozempic©). For example, maybe taking your weekly injection the beginning of your work week is the secret of continuing to live your life and enjoying these food/drink items without the gnarly side effects.

• Dip your toes in before diving head first. Start out by consuming a very small portion of alcohol, fried food, or carbonated beverages then reflect on how you feel afterwards. 
• Meal sizes. Consider eating smaller meals more frequently rather than a large meal at once. Don’t forget to incorporate more snacks with protein in them. 

Will these symptoms ever go away?! 

Symptoms should improve within 1-2 weeks of starting each new dose. But what if they’re still there after awhile?

• If signs and symptoms do not improve after 2 weeks: contact your provider. You can consider asking your provider to decrease the dose or pause the medication 
• If symptoms are ever severe and prevent you from going about your day to day routine: contact your provider. You can consider asking your provider to decrease the dose or pause the medication or potentially changing to a different medication

Weight Loss

Medications with this side effect

• Metformin (Glucophage©; pill)
• Tirzepatide (Mounjaro©; injection)
• Dulaglutide (Trulicity©; injection)
• Liraglutide (Victoza©; injection)
• Semaglutide (Ozempic©; injection)
• Semaglutide (Rybelsus©; pill)

Why does this happen? 

These medications lead to appetite suppression, meaning they will make you feel less hungry. Thesse meds in order from weakest to strongest include: metformin (Glucophage©) < dulaglutide (Trulicity©) < liraglutide (Victoza©) < semaglutide (Rybelsus©) < semaglutide (Ozempic©) < tirzepatide (Mounjaro©)

What should this look like?

You want SLOW weight loss. Fast weight loss is scary! This is because rapid weight loss increases risk of developing gallstones. Tell your provider if you are losing weight too quickly. 

What is too fast of weight loss you may ask? Weight loss is excessive if:

• More than 5% in one month (take your weight and multiply by 0.05 to see what that looks like for you) or
• > 2 lbs per week
• And
• Is accompanied by inability to complete day to day tasks because of severe, off-and-on pain in the upper right belly or upper middle stomach that can be so bad it makes people stop what they’re doing, move less, and avoid certain foods—especially fatty meals.

Remember, people experience side effects differently!

Keep in mind, most people have weight loss, however, everyone’s body is different. There are some who have very minimal weight loss and that’s okay, because there are other benefits these medications have for your health. Try to ask yourself, is it helping your diabetes management? Do you feel better? Is your risk of the scary complications from diabetes less now? Weight loss doesn’t have to be a goal on these meds, but it should be a part of the convo with your provider. If it has been a few months and you are not losing very much weight, make sure to bring this up to your provider.

Lower Blood Sugar (if you’re taking insulin)

Medications with this side effect

ALL noninsulin diabetes medications

Why does this happen? 

There is always a risk of low blood sugar if you take ANY non-insulin diabetes medication with insulin. Make sure you understand if you need to reduce your insulin dose if ever starting a new medication for diabetes that is not insulin.

With type 2 diabetes, some noninsulin diabetes medications lead to an increase in insulin production in your body, such as glimepiride (Amaryl©), glipizide (Glucotrol©), glyburide (Diabeta©), which increases your risk of low blood sugar, regardless if you take insulin shot(s) or not.

It is unlikely that other non-insulin diabetes medications mentioned would lead to low blood sugar if you were not taking insulin with them considering they do NOT cause a direct increase in insulin production, rather they work in different ways to lower sugar in your body (either by decreasing insulin resistance, improving insulin sensitivity, or preventing reabsorption of sugar back into the bloodstream). 

Is it the meds causing the lows, or something else?

Keep in mind, it can be challenging to know what caused your low at times. If it is ever thought to be from medication it will occur on a consistent basis (2 or more times at the same time). There are other things in your lifestyle that can lead to low blood sugars (examples: exercise, food poisoning, decrease in appetite/eating less often) as well that are important to rule out. One low blood sugar every once in a while is very typical for most and is less likely to be associated with your medication.

Need a refresher on how to manage low blood sugar? We’ve got you covered. Check out this article for the details.

In Conclusion

While you are determining if a medication is right for you, it is crucial to have open and honest communication with your healthcare provider. There are situations when one medication may not work well for you but you may tolerate a different one better (example: Trulicity caused you to have severe diarrhea, but it is possible to take Ozempic without diarrhea). It may be ideal to consider requesting close follow up with your provider, such as 1 month after starting a new medication, to have dedicated time to review how you are feeling after starting a new medication and discuss your options moving forward with your care. Remember, knowledge is power and your voice matters. Side effects can occur when taking any medication, but you do not have to deal with them alone. You deserve a plan that works best for you! 

Citations

1. American Diabetes Association Professional Practice Committee; 6. Glycemic Goals and Hypoglycemia: Standards of Care in Diabetes—2025. Diabetes Care 1 January 2025; 48 (Supplement_1): S128–S145. https://doi.org/10.2337/dc25-S006
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4. Matthews DR, Cull CA, Stratton IM, Holman RR, Turner RC. UKPDS 26: Sulphonylurea failure in non-insulin-dependent diabetic patients over six years. UK Prospective Diabetes Study (UKPDS) Group. Diabet Med. 1998 Apr;15(4):297-303. doi: 10.1002/(SICI)1096-9136(199804)15:4<297::AID-DIA572>3.0.CO;2-W. PMID: 9585394.