Short answer: In the label's 24-week trial of sitagliptin and metformin started together, the most common side effects were diarrhea (7.5% vs 4.0% on placebo), upper respiratory infection (6.2% vs 5.1%) and headache (5.9% vs 2.8%). Low blood sugar was more common when a sulfonylurea or insulin was added. Janumet has a boxed warning for lactic acidosis, a rare but sometimes fatal build-up of lactic acid from metformin.
What Janumet is approved for: Janumet combines sitagliptin, a DPP-4 inhibitor, with metformin, a biguanide. It is approved, along with diet and exercise, to improve blood sugar control in adults with type 2 diabetes (section 1). It should not be used in type 1 diabetes, and it has not been studied in people who have had pancreatitis.
Source
JANUMET (sitagliptin and metformin hydrochloride) tablets, for oral use, prescribing information and Medication Guide. Merck Sharp & Dohme. DailyMed, version published August 27, 2026. DailyMed setid d19c7ed0-ad5c-426e-b2df-722508f97d67
WARNING: LACTIC ACIDOSIS
Cases of metformin-associated lactic acidosis reported after approval have resulted in death, low body temperature, low blood pressure and slow heart rhythms that resist treatment. It often starts subtly, with only vague symptoms such as feeling unwell, muscle aches, trouble breathing, sleepiness and abdominal pain. It was marked by blood lactate above 5 mmol/L, anion gap acidosis without ketones, a raised lactate to pyruvate ratio, and metformin levels generally above 5 mcg/mL. Risk factors include kidney impairment, certain drugs (for example carbonic anhydrase inhibitors such as topiramate), age 65 or older, a radiology study with contrast, surgery and other procedures, low-oxygen states such as acute heart failure, heavy alcohol use, liver impairment and mitochondrial diseases. If it is suspected, Janumet is stopped immediately and supportive care is started in a hospital; prompt hemodialysis is recommended.
These are the label's own numbers from the Adverse Reactions section. Where the label compares with placebo (a dummy treatment), both columns are shown, so you can see how much more often a reaction happened on Janumet.
| Adverse reaction | Placebo (N = 176) | Sitagliptin 100 mg once daily (N = 179) | Metformin HCl 500 mg or 1000 mg twice daily (N = 364) | Sitagliptin 50 mg twice daily + Metformin HCl 500 mg or 1000 mg twice daily (N = 372) |
|---|---|---|---|---|
| Diarrhea | 7 (4.0) | 5 (2.8) | 28 (7.7) | 28 (7.5) |
| Upper Respiratory Tract Infection | 9 (5.1) | 8 (4.5) | 19 (5.2) | 23 (6.2) |
| Headache | 5 (2.8) | 2 (1.1) | 14 (3.8) | 22 (5.9) |
Number of patients (%), intent-to-treat population, in a 24-week placebo-controlled factorial study. The metformin columns pool people given 500 mg or 1,000 mg twice daily.
| Add-on study (24 weeks) and measure | Sitagliptin 100 mg arm | Placebo arm |
|---|---|---|
| With metformin + glimepiride, N = 116 vs 113: Overall, n (%) | 19 (16.4) | 1 (0.9) |
| With metformin + glimepiride: Rate (episodes/patient-year) | 0.82 | 0.02 |
| With metformin + glimepiride: Severe, n (%) | 0 (0.0) | 0 (0.0) |
| With metformin + insulin, N = 229 vs 233: Overall, n (%) | 35 (15.3) | 19 (8.2) |
| With metformin + insulin: Rate (episodes/patient-year) | 0.98 | 0.61 |
| With metformin + insulin: Severe, n (%) | 1 (0.4) | 1 (0.4) |
Based on all reports of symptomatic low blood sugar; a glucose reading was not required. Rate counts every episode, so one person can have several. Severe means needing medical help, or with reduced consciousness or a seizure.
Stomach side effects in the same starting trial (Table 2): nausea 4.8% on sitagliptin plus metformin vs 1.1% on placebo, vomiting 2.2% vs 0.6%, and abdominal pain 3.0% vs 2.3%. When sitagliptin was added to metformin alone, diarrhea was 2.4% vs 2.5% on placebo plus metformin.
When sitagliptin was added to metformin alone for 24 weeks, no side effect was seen in at least 5% and more often than on placebo. Stopping for side effects was 1.9% vs 2.5%.
Added to metformin and glimepiride, headache was 6.9% on sitagliptin vs 2.7% on placebo. Added to metformin and rosiglitazone through week 18, upper respiratory infection was 5.5% vs 5.2% and stuffy or runny nose 6.1% vs 4.1%.
Low blood sugar when started with diet and exercise only: 0.6% on placebo, 0.6% on sitagliptin alone, 0.8% on metformin alone and 1.6% on the two together. Added to metformin alone: 1.3% vs 2.1% on placebo.
In metformin trials of 29 weeks, previously normal vitamin B12 levels fell below normal in about 7% of people.
Reported after approval, with frequency unknown: allergic reactions including anaphylaxis, angioedema, rash, hives and Stevens-Johnson syndrome; liver enzyme rises and liver injury; pancreatitis; worsening kidney function including acute kidney failure; severe joint pain; bullous pemphigoid; constipation; vomiting; headache; muscle pain; back pain; itching; mouth ulcers; and rhabdomyolysis.
The Warnings and Precautions part of the label lists these. Each line gives the label's heading and what it means in plain words.
Lactic acidosis. The boxed-warning risk. Janumet is not used with an eGFR below 30 and is not recommended at 30 to under 45. eGFR is checked before starting and at least yearly, more often in older people. Janumet is stopped around some iodinated contrast scans, paused while food and fluids are restricted for surgery, stopped in shock, heart attack, sepsis or acute heart failure with low oxygen, avoided with liver disease, and not recommended with mitochondrial diseases such as MELAS and MIDD.
Pancreatitis. Acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, has been reported after approval. People are watched for signs after starting, and Janumet is stopped promptly if pancreatitis is suspected.
Heart failure. Heart failure was linked to two other DPP-4 inhibitors in heart outcome trials. Risks and benefits are weighed before starting in people at risk, such as those with past heart failure or kidney problems, and they are watched for symptoms.
Acute kidney failure. Worsening kidney function, including acute kidney failure sometimes needing dialysis, has been reported. Kidney function is checked before starting and at least yearly, and more often where kidney problems are expected.
Vitamin B12 deficiency. Metformin may lower vitamin B12. Blood counts are measured yearly and vitamin B12 every 2 to 3 years.
Low blood sugar with insulin or a sulfonylurea. Janumet may raise the risk of low blood sugar with insulin or a medicine that makes the body release insulin, such as a sulfonylurea, so a lower dose of those may be needed.
Allergic reactions. Serious allergic reactions to sitagliptin, including anaphylaxis, angioedema and Stevens-Johnson syndrome, have been reported, mostly within the first 3 months and some after the first dose. Janumet is stopped if one is suspected.
Severe and disabling joint pain. Severe joint pain has been reported with DPP-4 inhibitors, starting anywhere from one day to years after starting. It eased after stopping, and in some people came back on restarting.
Bullous pemphigoid. A blistering skin condition needing hospital care has been reported with DPP-4 inhibitors. Janumet is stopped if bullous pemphigoid is suspected.
From the Medication Guide that comes with Janumet:
Dose Track has a side-effect log. Each entry records the symptom, a severity (none, mild, moderate, severe or life-threatening), the date and an optional note, and can be tied to a specific dose or logged on its own. The history screen shows what you logged over time, which makes it easier to tell your prescriber when a reaction started and whether it is easing. The app records what you enter; it does not judge whether a symptom is serious. For anything on the label's call-your-doctor list, call your doctor.
This page is what the FDA label says, in plain words. It is not medical advice. Follow your prescriber, and ask them or your pharmacist about anything here.