Januvia vs Tradjenta: Sitagliptin and Linagliptin Compared, Including Kidney Dosing and 2026 Prices

Januvia (sitagliptin) and Tradjenta (linagliptin, sold as Trajenta outside the US) are the two best known DPP-4 inhibitors, the once-daily tablets that raise the body's own incretin hormones to lower blood sugar. Their blood sugar lowering is almost identical and both proved heart-safe in large trials. The real differences are how they leave the body and what that means for kidney function: sitagliptin is cleared by the kidneys and needs a lower dose as kidney function falls, while linagliptin is cleared mostly through the gut and uses one 5 mg dose for everyone. In 2026 there is also a price difference in the US: generic sitagliptin went on sale in the middle of the year, and linagliptin still has no generic in pharmacies.

This guide compares the two using their current US prescribing information, the TECOS, CARMELINA and CAROLINA outcome trials, the Medicaid NADAC price survey and Medicare's negotiated prices. Sources are listed at the end.

The short answer

If your kidneys work normally, Januvia 100 mg and Tradjenta 5 mg do the same job: each lowered HbA1c by about 0.6 to 0.8 points more than placebo in its monotherapy trials, neither causes low blood sugar on its own, and neither raised heart attack, stroke or heart failure risk in outcome trials. Tradjenta is simpler when kidney function is reduced or changing, because its dose never changes. Januvia needs 50 mg below an eGFR of 45 and 25 mg below 30. In the US, generic sitagliptin now costs pharmacies about a third of brand Januvia, which makes sitagliptin the cheaper option for most people paying out of pocket.

How DPP-4 inhibitors work

After a meal the gut releases incretin hormones (GLP-1 and GIP) that tell the pancreas to release insulin and hold back glucagon, but only while blood sugar is raised. The enzyme DPP-4 breaks those hormones down within minutes. Blocking DPP-4 keeps them active for longer, so insulin rises when it is needed and falls when it is not. That glucose-dependent action is why DPP-4 inhibitors rarely cause low blood sugar unless they are combined with insulin or a sulfonylurea.

The effect is milder than an injected GLP-1 drug such as semaglutide, which drives the GLP-1 receptor much harder. DPP-4 inhibitors are generally weight neutral and nausea was not among their common side effects in trials.

Januvia and Tradjenta at a glance

	Januvia (sitagliptin)	Tradjenta (linagliptin)
Maker	Merck (MSD outside the US)	Boehringer Ingelheim
Approved use	Blood sugar control in adults with type 2 diabetes, with diet and exercise	Same
Tablet strengths	25 mg, 50 mg, 100 mg	5 mg only
Usual dose	100 mg once daily	5 mg once daily
Food	With or without food	With or without food
Kidney dose changes	Yes, below eGFR 45	None
Liver dose changes	None needed in moderate impairment; not studied in severe	None
Children	Not effective in trials in ages 10 to 17	Not effective in a trial in ages 10 to 17
Type 1 diabetes	Should not be used	Not recommended

Dosing and kidney function

This is the practical difference that decides the choice for many people.

Kidney function (eGFR, mL/min/1.73 m²)	Januvia dose	Tradjenta dose
45 or above	100 mg once daily	5 mg once daily
30 to 44	50 mg once daily	5 mg once daily
Below 30	25 mg once daily	5 mg once daily
Dialysis	25 mg once daily, any time relative to dialysis	No kidney dose change; no dialysis-specific dose, and the label notes dialysis is unlikely to remove linagliptin

The Januvia label asks for kidney function to be checked before starting and periodically afterwards, more often in older people. It also lists acute kidney failure in its warnings, noting that some reported cases involved people with kidney impairment given too high a dose. The Tradjenta label has no kidney dose adjustment, but it warns that using linagliptin with insulin in severe kidney impairment was associated with more low blood sugar. In the CARMELINA trial, 63% of the people given linagliptin had an eGFR below 60, and about 15% of all participants were below 30.

Why the kidney rules differ

	Sitagliptin	Linagliptin
Absolute bioavailability	About 87%	About 30%
Time to peak level	1 to 4 hours	About 1.5 hours
Half-life	About 12.4 hours	Effective half-life about 12 hours; terminal phase over 100 hours because it binds tightly to DPP-4
How it leaves the body	About 79% unchanged in urine	About 80% through bile and faeces, about 5% in urine
Exposure in severe kidney impairment	Higher, hence the lower doses	About 40% higher, not considered to need a dose change

Because sitagliptin depends on the kidneys to leave the body, falling kidney function makes it build up, so the dose is cut to keep blood levels in range. Linagliptin barely uses the kidneys. Its exposure still rises, by about 71% in moderate and 42% in severe kidney impairment in the label's study, but the label does not consider that to need a dose change. Neither is a kidney-protective drug: in CARMELINA, linagliptin had no effect on a combined kidney outcome (hazard ratio 1.04). For kidney protection, the outcome trial evidence sits with the SGLT2 inhibitors covered in our Jardiance vs Farxiga comparison.

Blood sugar lowering compared

Each label reports two placebo-controlled monotherapy trials, one of 18 weeks and one of 24 weeks, in people starting at an HbA1c of about 8%.

Monotherapy trial	Difference from placebo in HbA1c	Reached HbA1c under 7%	Placebo reaching under 7%
Januvia 100 mg, 18 weeks	-0.6	36%	16%
Januvia 100 mg, 24 weeks	-0.8	41%	17%
Tradjenta 5 mg, 18 weeks	-0.6	23.5%	11.8%
Tradjenta 5 mg, 24 weeks	-0.7	25%	12%

The placebo-adjusted drop is the fairer number because each trial had its own patients and its own placebo response. On that measure the two are within a tenth of a point. The difference in the share reaching an HbA1c under 7% partly reflects the different populations and trial designs, not a proven difference in strength. No large head-to-head trial has shown one to be more effective.

Side effects compared

Both are among the best tolerated diabetes tablets. The common side effects barely separate from placebo.

Adverse reaction	Drug	Placebo	Source
Nasopharyngitis	Januvia 5.2%	3.3%	Januvia monotherapy trials
Nasopharyngitis	Tradjenta 7.0%	6.1%	14 pooled Tradjenta trials
Diarrhoea	Tradjenta 3.3%	3.0%	14 pooled Tradjenta trials
Cough	Tradjenta 2.1%	1.4%	14 pooled Tradjenta trials
Headache (with glimepiride)	Januvia 5.9%	2.3%	Januvia add-on to glimepiride

The overall rate of side effects on Januvia was similar to placebo in its monotherapy, metformin and glitazone trials. When it was added to glimepiride the overall rate was higher, partly because of more low blood sugar episodes.

Warnings both labels share

• Pancreatitis. Acute pancreatitis, including fatal cases, has been reported with both. In CARMELINA it occurred in 0.3% on linagliptin against 0.1% on placebo, and two people on linagliptin died of it. Severe, persistent abdominal pain, sometimes spreading to the back, means stop the drug and get checked. Neither drug has been studied in people with a history of pancreatitis. In the Tradjenta trial programme, pancreatitis was reported at 15.2 cases per 10,000 patient-years against 3.7 on comparators.
• Heart failure. Both labels carry a class warning because two other DPP-4 inhibitors were linked to heart failure in outcome trials. Sitagliptin and linagliptin themselves did not raise heart failure admissions in theirs (see below).
• Serious allergic reactions. Both labels list anaphylaxis, angioedema and exfoliative skin conditions (Januvia names Stevens-Johnson syndrome), usually within the first 3 months and sometimes after the first dose. Both drugs are contraindicated after a serious allergic reaction to them.
• Severe joint pain. Disabling arthralgia has been reported with the whole class, starting anywhere from a day to years after starting, and settling after stopping.
• Bullous pemphigoid. Cases of this blistering skin disease needing hospital treatment have been reported with DPP-4 inhibitors; in CARMELINA it occurred in 0.2% on linagliptin and none on placebo. Report new blisters or skin erosions; the drug should be stopped if bullous pemphigoid is suspected.
• Low blood sugar with insulin or sulfonylureas. A lower dose of the insulin or sulfonylurea may be needed.

Two label-specific points: Januvia carries an extra acute kidney failure warning tied to its kidney clearance. Tradjenta's effect can be cut by strong inducers of the P-gp pump or the CYP3A4 enzyme, such as rifampin, and its label strongly recommends a different treatment in that situation.

Heart and kidney outcome trials

TECOS (sitagliptin) added sitagliptin or placebo to usual care in 14,671 adults with type 2 diabetes and established cardiovascular disease, followed for a median of 3.0 years. The primary outcome (cardiovascular death, heart attack, stroke or hospital admission for unstable angina) occurred in 11.4% on sitagliptin and 11.6% on placebo, a hazard ratio of 0.98. Heart failure admissions were identical (hazard ratio 1.00).

CARMELINA (linagliptin) tested linagliptin against placebo in 6,979 adults at high heart and kidney risk, over a median of 2.2 years. MACE occurred in 12.4% against 12.1% (hazard ratio 1.02), and the combined kidney outcome in 9.4% against 8.8% (hazard ratio 1.04). Hypoglycaemia was reported in 29.7% against 29.4%, a reminder that most of these patients were also on insulin or other diabetes drugs.

CAROLINA (linagliptin) is the unusual one: it compared linagliptin with an active drug, the sulfonylurea glimepiride, in 6,033 adults over a median of 6.3 years. MACE was 11.8% against 12.0% (hazard ratio 0.98), so linagliptin was as safe for the heart as glimepiride.

SAVOR-TIMI 53 (saxagliptin), a different DPP-4 inhibitor sold as Onglyza, is one of the trials behind the class heart failure warning, which both labels attribute to two other DPP-4 inhibitors: heart failure admissions were 3.5% against 2.8% on placebo, a hazard ratio of 1.27.

The pattern is clear: sitagliptin and linagliptin are neutral for the heart. They neither protect against nor add to cardiovascular events or heart failure. That is different from the SGLT2 inhibitors and GLP-1 drugs, several of which reduced cardiovascular or kidney events in their outcome trials. For someone who needs heart or kidney protection, a DPP-4 inhibitor is not the tool for that job.

Low blood sugar: what CAROLINA showed

CAROLINA's most useful finding for everyday decisions is not about the heart. Over 6.3 years, 10.6% of people on linagliptin had at least one hypoglycaemic event, against 37.7% on glimepiride (hazard ratio 0.23).

That is the main reason DPP-4 inhibitors are often chosen over sulfonylureas as the second tablet after metformin, particularly for older people, people who drive for work, and anyone living alone. Sitagliptin shows the same pattern. In a 52-week trial in its label, low blood sugar occurred in 4.9% on sitagliptin against 32.0% on glipizide, and in the 5-year GRADE trial severe low blood sugar was 0.7% on sitagliptin against 2.2% on glimepiride. Our comparison of metformin and glimepiride explains why sulfonylureas cause low blood sugar.

Combination tablets

Both drugs are sold combined with metformin, which is the usual first-line medicine. Januvia with metformin is Janumet; linagliptin with metformin is Jentadueto in the US and Trajenta Duo in India. Both are also paired with SGLT2 inhibitors in some markets.

We stock Janumet 50mg/500mg, Janumet 50mg/1000mg, Janumet XR, Trajenta Duo 2.5mg/500mg, Trajenta Duo 2.5mg/850mg and Trajenta Duo 2.5mg/1000mg, as well as linagliptin with dapagliflozin (Oxra-L) and sitagliptin with dapagliflozin (Oxra-S 10/100). Janumet is taken twice daily with meals, up to 100 mg of sitagliptin a day, and Trajenta Duo contains 2.5 mg of linagliptin per tablet, taken twice daily, so the daily DPP-4 dose matches the single tablets. Janumet is not recommended at an eGFR of 30 to 44, because its sitagliptin dose cannot be lowered, and it is contraindicated below 30 because of its metformin. Like other metformin products, Janumet carries a boxed warning for lactic acidosis. The metformin in any combination counts toward the daily metformin limit covered in our metformin dosage guide.

Other DPP-4 inhibitors

Three more DPP-4 inhibitors are sold outside the US and are common in India: vildagliptin (Vysov 50mg), teneligliptin (Ziten 20mg) and saxagliptin (Onglyza 5mg, Onglyza 2.5mg). Saxagliptin is FDA-approved; vildagliptin and teneligliptin are not approved in the US. Saxagliptin is the one with the heart failure signal in SAVOR-TIMI 53. For people outside the US these can be reasonable options, but the outcome trial evidence is strongest for sitagliptin and linagliptin.

Generic availability in the US

Sitagliptin: Merck settled patent challenges so that generic Januvia and Janumet could launch in the US in May 2026 and generic Janumet XR in July 2026. Generic sitagliptin phosphate tablets first appeared in the NADAC pharmacy cost file on 5 August 2026, in 25 mg, 50 mg and 100 mg, along with sitagliptin-metformin tablets. A separate product, Zituvio (sitagliptin), was approved in October 2023 through its own new drug application rather than as a generic of Januvia.

Linagliptin: The FDA database lists several approved generic linagliptin applications, but none appeared in the NADAC pharmacy file as of September 2026, so pharmacies were still buying only brand Tradjenta.

What they cost in the US

Product (week of 23 September 2026)	Pharmacy cost per tablet	30 tablets
Tradjenta 5 mg	$16.79819	$503.95
Januvia 100 mg	$10.55179	$316.55
Generic sitagliptin 100 mg	$3.77084	$113.13
Generic sitagliptin 50 mg	$3.68380	$110.51
Generic sitagliptin 25 mg	$3.46931	$104.08

These are the prices pharmacies pay according to the Medicaid NADAC survey, not retail prices. Generic sitagliptin is new to the US market, so check current prices. In September 2026 it cost pharmacies about 36% of brand Januvia and about 22% of Tradjenta.

Medicare's negotiated prices

Drug	List price, 30 days	Medicare negotiated price, 30 days	In force from
Januvia	$527 (2023)	$113	1 January 2026
Tradjenta	$488 (2024)	$78	1 January 2027
Janumet and Janumet XR	$526 (2024)	$80	1 January 2027

Januvia was in the first round of Medicare drug price negotiation; Tradjenta and Janumet were in the second. The negotiated price is what Medicare Part D plans pay; your share still depends on your plan.

Which one fits which situation

Situation	Better fit
Normal kidney function, cost matters, US	Generic sitagliptin
eGFR below 45, or kidney function changing	Linagliptin (no dose change), or sitagliptin at the reduced dose
On dialysis	Sitagliptin has a labelled dialysis dose (25 mg); the linagliptin label gives no dialysis-specific advice, so ask the kidney specialist
Taking rifampin or another strong CYP3A4 or P-gp inducer	Sitagliptin (Tradjenta label advises an alternative)
Needs heart or kidney protection	Neither alone; consider an SGLT2 inhibitor or GLP-1 drug
Wants to avoid hypoglycaemia as the second drug after metformin	Either, rather than a sulfonylurea
History of pancreatitis	Neither was studied; discuss alternatives
History of heart failure	Either with monitoring; saxagliptin had a heart failure signal in its outcome trial

Switching between them

Neither label gives switching instructions. Both drugs block the same enzyme, so a switch means stopping one and starting the other at its usual labelled dose (Januvia 100 mg, or the kidney-adjusted dose, or Tradjenta 5 mg), not overlapping them. Never take two DPP-4 inhibitors together. Both labels also advise caution in anyone who had angioedema with another DPP-4 inhibitor.

What we stock

We carry the Indian-market originals of both brands: Januvia 100mg, Januvia 50mg and Januvia 25mg made by MSD, and Trajenta 5mg made by Boehringer Ingelheim. Both are prescription medicines in the US, UK, Canada and Australia. With US generic sitagliptin now on sale, a US patient paying cash should compare local generic prices before ordering from abroad; our guide to cross-border pharmacy rules explains what US law allows. For the wider picture of diabetes treatment options, see our type 2 diabetes overview.

Sources

• JANUVIA (sitagliptin) US prescribing information, Merck Sharp and Dohme (current DailyMed listing, text revised July 2023): sections 1, 2, 4, 5, 6.1, 8, 12.3 and 14 (Tables 1 and 6). DailyMed
• TRADJENTA (linagliptin) US prescribing information, Boehringer Ingelheim, March 2025: sections 1, 2, 5, 6.1, 7, 8, 12.3 and 14 (Tables 1, 5, 13 and 14). DailyMed
• Green JB et al. Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes (TECOS). N Engl J Med 2015;373(3):232-42. PMID 26052984.
• Rosenstock J et al. Effect of linagliptin vs placebo on major cardiovascular events in adults with type 2 diabetes and high cardiovascular and renal risk (CARMELINA). JAMA 2019;321(1):69-79. PMID 30418475.
• Rosenstock J et al. Effect of linagliptin vs glimepiride on major adverse cardiovascular outcomes in patients with type 2 diabetes (CAROLINA). JAMA 2019;322(12):1155-1166. PMID 31536101.
• GRADE Study Research Group (Nathan DM et al). Glycemia reduction in type 2 diabetes: glycemic outcomes. N Engl J Med 2022;387(12):1063-1074. PMID 36129996.
• Scirica BM et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus (SAVOR-TIMI 53). N Engl J Med 2013;369(14):1317-26. PMID 23992601.
• Merck and Co. Form 10-Q for the quarter ended 31 March 2026: Januvia, Janumet and Janumet XR patent settlements. SEC
• US Food and Drug Administration. Drugs@FDA: ZITUVIO NDA 211566; linagliptin applications. Accessed via the openFDA drugsfda API, September 2026.
• Centers for Medicare and Medicaid Services. National Average Drug Acquisition Cost (NADAC) 2026 file, as of 23 September 2026. data.medicaid.gov
• Centers for Medicare and Medicaid Services. Negotiated prices fact sheets for initial price applicability years 2026 and 2027. CMS 2026, CMS 2027

This article is for information only and is not medical advice. Januvia and Tradjenta are prescription medicines. Do not start, stop or switch diabetes medicines without your prescriber, who needs your current kidney function and full medicine list. Severe abdominal pain, blistering or a swollen face or throat need urgent medical care.