Januvia
Indications
Sitagliptin is FDA-approved as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. It was the first dipeptidyl peptidase-4 (DPP-4) inhibitor approved in the United States (October 2006). Cardiovascular safety in patients with established atherosclerotic disease was established by the TECOS trial (n=14,671), which demonstrated non-inferiority to placebo for the primary composite cardiovascular endpoint with no increase in heart-failure hospitalization.
| Indication | Approved Population | Therapy Type | Status |
|---|---|---|---|
| Type 2 diabetes — glycemic control | Adults (≥18 years) | Adjunct to diet and exercise; mono- or combination | FDA Approved |
| Combination with metformin, sulfonylureas, thiazolidinediones, SGLT2 inhibitors, or insulin | Adults inadequately controlled on monotherapy | Add-on therapy | FDA Approved |
| Pediatric type 2 diabetes | Patients aged 10–17 years | Mono- or combination | Not Approved |
| Inpatient hyperglycemia management | Hospitalized adults with mild-to-moderate hyperglycemia | Adjunctive (selected cases) | Off-Label |
Sitagliptin should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis. The labeling explicitly notes the drug has not been studied in patients with a history of pancreatitis. Within current treatment algorithms, DPP-4 inhibitors generally occupy a third- or fourth-line role behind metformin, GLP-1 receptor agonists, and SGLT2 inhibitors — particularly in patients with established cardiovascular disease, heart failure, or chronic kidney disease, where the latter classes provide organ-protective benefits that DPP-4 inhibitors do not.
Pediatric T2DM (Evidence: Negative) — Three placebo-controlled studies in adolescents aged 10–17 years (n=410) did not demonstrate efficacy significantly different from placebo. In December 2020, the FDA approved labeling changes stating that sitagliptin is not proven to improve glycemic control in children aged 10 to 17 with type 2 diabetes.
Inpatient hyperglycemia (Evidence: Low–Moderate) — Small studies in hospitalized non-critically ill patients suggest acceptable efficacy as an adjunct to basal insulin in selected cases with mild hyperglycemia and adequate beta-cell function; not a replacement for insulin in moderate-to-severe hyperglycemia or in surgical or critical care settings.
Cardiovascular benefit (Evidence: Negative) — TECOS established cardiovascular safety but did not demonstrate cardiovascular benefit. Sitagliptin should not be selected for the purpose of MACE reduction; GLP-1 receptor agonists or SGLT2 inhibitors are preferred when CV risk reduction is a treatment goal.
Dosing
The standard adult dose of sitagliptin is 100 mg orally once daily, taken with or without food. The drug is renally cleared, and dose reduction is required for moderate or worse renal impairment. Assess renal function at baseline and periodically thereafter. Combination with insulin or sulfonylureas warrants pre-emptive dose reduction of those agents to mitigate hypoglycemia.
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| T2DM — adult, normal renal function (eGFR ≥45) | 100 mg PO daily | 100 mg PO daily | 100 mg PO daily | No titration required. Take with or without food at the same time daily. Expected HbA1c reduction: ~0.5–0.8% as monotherapy. |
| Moderate renal impairment (eGFR 30 to <45) | 50 mg PO daily | 50 mg PO daily | 50 mg PO daily | Half-dose to compensate for reduced renal clearance. Reassess renal function periodically. |
| Severe renal impairment (eGFR <30) or ESRD on dialysis | 25 mg PO daily | 25 mg PO daily | 25 mg PO daily | Quarter-dose. May be administered without regard to dialysis timing. Inappropriate dosing in CKD has been linked to AKI in postmarketing reports. |
| Concurrent insulin or sulfonylurea | 100 mg PO daily (renal-adjusted) | 100 mg PO daily (renal-adjusted) | 100 mg PO daily (renal-adjusted) | Reduce insulin or sulfonylurea dose at initiation to reduce hypoglycemia risk. Hypoglycemia incidence rises to 12–16% with these combinations. |
| Hepatic impairment — mild to moderate (Child-Pugh ≤9) | 100 mg PO daily | 100 mg PO daily | 100 mg PO daily | No adjustment needed. Limited clinical experience in severe hepatic impairment (Child-Pugh >9). |
| Older adults (≥65 years) | Per renal function | Per renal function | 100 mg PO daily | No age-based adjustment. Renal function declines with age — assess eGFR before initiation and at least annually. |
| Missed dose | Take as soon as remembered the same day | If almost time for next dose, skip and resume regular schedule. Do not double dose. | ||
Postmarketing acute kidney injury — sometimes requiring dialysis — has been reported with sitagliptin, often associated with inappropriate dosing in patients with reduced renal function. Always check eGFR before prescribing or refilling, and adjust the dose promptly when renal function declines. Patients with chronic kidney disease may have stable creatinine yet significantly reduced eGFR; rely on calculated eGFR rather than serum creatinine alone.
Within the DPP-4 inhibitor class, sitagliptin and linagliptin both demonstrated cardiovascular safety in dedicated outcomes trials (TECOS, CARMELINA). Saxagliptin and alogliptin showed an excess of heart-failure hospitalization in SAVOR-TIMI 53 and EXAMINE respectively, leading to FDA labeling changes. Linagliptin requires no renal dose adjustment, which can simplify management in advanced CKD.
Pharmacology
Mechanism of Action
Sitagliptin is a competitive, reversible inhibitor of dipeptidyl peptidase-4 (DPP-4), the enzyme that degrades the endogenous incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). By blocking DPP-4 activity by approximately 80% over 24 hours at the 100 mg dose, sitagliptin prolongs the post-prandial action of these incretins, producing approximately a two- to three-fold increase in active GLP-1 concentrations. The downstream consequences include glucose-dependent stimulation of insulin secretion from pancreatic beta cells and suppression of inappropriately elevated post-prandial glucagon release from alpha cells. Because the insulinotropic effect is glucose-dependent, sitagliptin used as monotherapy carries a low intrinsic risk of hypoglycemia.
Unlike GLP-1 receptor agonists, sitagliptin does not produce supraphysiologic GLP-1 levels and is therefore weight-neutral, with no meaningful effect on gastric emptying or appetite. Expected HbA1c reduction is approximately 0.5–0.8% as monotherapy or add-on therapy, smaller than that achieved with GLP-1 receptor agonists or SGLT2 inhibitors. The TECOS trial confirmed cardiovascular safety in patients with established atherosclerotic disease but did not demonstrate cardiovascular benefit, distinguishing this class from GLP-1 receptor agonists and SGLT2 inhibitors.
ADME Profile
| Parameter | Value | Clinical Implication |
|---|---|---|
| Absorption | Bioavailability ~87%; Tmax 1–4 hours; food has no effect | Convenient once-daily oral dosing without food restrictions or titration. |
| Distribution | Vd ~198 L; ~38% reversibly protein-bound (low) | Wide tissue distribution. Low protein binding limits displacement-type interactions. |
| Metabolism | Limited hepatic metabolism (primarily CYP3A4, contribution from CYP2C8); ~79% excreted unchanged in urine | Minor PK changes only with strong CYP3A4 inhibitors. Not a meaningful CYP inhibitor or inducer. |
| Elimination | Primarily renal via active tubular secretion (OAT3, P-gp); t½ ~12.4 h (range 8–14 h); renal clearance ~388 mL/min | Mandatory renal dose adjustment when eGFR <45 mL/min/1.73 m². Modestly removed by hemodialysis (~13.5%); timing of dose around dialysis not required. |
Side Effects
Sitagliptin is generally well tolerated, with overall adverse-reaction rates in placebo-controlled trials similar to placebo when used as monotherapy or with metformin. Frequencies below are derived from the FDA-approved labeling pooled placebo-controlled trial data and the post-approval TECOS cardiovascular outcomes trial. The most clinically relevant adverse reactions cluster into hypoglycemia (when combined with insulin or sulfonylureas), upper respiratory tract symptoms, and class-related immunologic and renal events.
| Adverse Effect | Incidence (Placebo) | Clinical Note |
|---|---|---|
| Hypoglycemia (with insulin ± metformin) | 15.5% (7.8%) | 24-week trial. Severe hypoglycemia 0.6% vs 0.3% placebo. Rate 1.06 vs 0.51 events/patient-year. Reduce insulin dose at initiation. |
| Hypoglycemia (with glimepiride ± metformin) | 12.2% (1.8%) | 24-week trial. Rate 0.59 vs 0.24 events/patient-year. Consider reducing or stopping the sulfonylurea. |
| Upper respiratory tract infection (54 wk, with metformin + rosiglitazone) | 15.5% (6.2%) | Reflects accumulated reporting over a longer treatment duration; symptomatic care typically sufficient. |
| Nasopharyngitis (54 wk, with metformin + rosiglitazone) | 11.0% (9.3%) | Modest excess over placebo; consistent class observation across DPP-4 inhibitors. |
| Adverse Effect | Incidence (Placebo) | Clinical Note |
|---|---|---|
| Peripheral edema (54 wk, with metformin + rosiglitazone) | 8.3% (5.2%) | Largely attributable to thiazolidinedione co-administration; reassess fluid status. |
| Upper respiratory infection (24 wk add-ons) | 5.5–6.3% (3.4–5.2%) | Mild and self-limited in most patients. |
| Nasopharyngitis (monotherapy / 24 wk add-ons) | 5.2–6.3% (3.3–4.6%) | No specific intervention typically required. |
| Headache (combination therapy) | 5.1–5.9% (2.3–3.9%) | Usually mild; consider alternate causes if persistent or severe. |
| Hypoglycemia (with metformin + rosiglitazone, 54 wk) | 3.9% (1.0%) | Modest excess; counsel patients on recognition and treatment. |
| Diarrhea (pooled monotherapy/metformin/pioglitazone add-ons) | 3.0% (2.3%) | Typically mild; not clinically distinguishable from placebo in most settings. |
| Abdominal pain (pooled) | 2.3% (2.1%) | Severe or persistent abdominal pain → exclude pancreatitis. |
| Hypoglycemia (monotherapy / metformin / pioglitazone) | 1.2% (0.9%) | No meaningful excess outside combination with insulin or sulfonylureas. |
| Nausea (pooled) | 1.4% (0.6%) | Usually mild; rarely treatment-limiting. |
| Adverse Effect | Estimated Frequency | Typical Onset | Required Action |
|---|---|---|---|
| Acute pancreatitis (including hemorrhagic / necrotizing) | 0.1 / 100 patient-years (no excess vs control in pooled analysis of 19 trials) | Any time after initiation | Discontinue immediately if suspected; check lipase; do not restart if confirmed. |
| Acute kidney injury / worsening renal function | Postmarketing reports (frequency unknown); sometimes requiring dialysis | Variable | Hold, assess volume status and renal function. Cautious reinitiation only if alternate etiology likely. |
| Tubulointerstitial nephritis | Postmarketing (rare) | Weeks–months | Discontinue if rising creatinine, sterile pyuria, or eosinophilia; nephrology referral. |
| Anaphylaxis / angioedema | Postmarketing (rare) | Within first 3 months (some after first dose) | Discontinue permanently; emergency care; contraindication to re-challenge. |
| Stevens-Johnson syndrome / exfoliative skin reactions | Postmarketing (rare) | Within first 3 months | Discontinue immediately; dermatology and emergency referral. |
| Bullous pemphigoid | Postmarketing (rare); class effect | Months to years | Discontinue; dermatology referral; topical or systemic immunosuppressives often needed. |
| Severe and disabling arthralgia | Postmarketing (rare); class effect | 1 day to years | Discontinue; symptoms typically resolve. Avoid re-challenge with any DPP-4 inhibitor. |
| Heart failure (class concern) | No excess in TECOS (HHF HR 0.94, 95% CI 0.78–1.13 after re-adjudication) | Variable | Consider risks/benefits in patients with prior HF and renal impairment; discontinue if HF develops. |
| Severe hypoglycemia (with insulin) | 0.6% vs 0.3% placebo | Days–weeks | Pre-emptively reduce insulin dose. Educate on recognition and glucagon use. |
| Hepatic enzyme elevations | Postmarketing (uncommon) | Variable | Monitor LFTs if symptomatic; consider discontinuation for significant elevation. |
| Reason for Discontinuation | Pattern | Context |
|---|---|---|
| Hypersensitivity / skin reactions | Rare but immediate | Onset typically within first 3 months. Permanent contraindication to re-challenge. |
| Hypoglycemia in combination therapy | Variable | Often resolved by reducing insulin or sulfonylurea rather than stopping sitagliptin. |
| Severe arthralgia | Rare | Resolves on discontinuation. Consider as cause of new joint pain in any DPP-4 inhibitor user. |
| Lack of glycemic efficacy | Variable | Modest HbA1c reduction (~0.5–0.8%) may be insufficient when targets are not met; switch to GLP-1 RA or SGLT2i often considered. |
Three distinctive DPP-4-class adverse events deserve clinical vigilance: severe arthralgia (consider as a cause of new or worsening joint pain regardless of drug duration; FDA Drug Safety Communication 2015), bullous pemphigoid (subepidermal blistering disorder; counsel patients to report new blisters or erosions), and hypersensitivity reactions including SJS (most often within the first 3 months). Each requires immediate discontinuation; arthralgia and bullous pemphigoid frequently resolve following drug withdrawal.
Drug Interactions
Sitagliptin has a clean pharmacokinetic interaction profile. It undergoes only limited hepatic metabolism (primarily CYP3A4, with minor CYP2C8 contribution), is not a meaningful CYP inhibitor or inducer, and demonstrated no clinically relevant pharmacokinetic interaction with metformin, glyburide, simvastatin, rosiglitazone, warfarin, or oral contraceptives in dedicated studies. The clinically significant interactions are therefore confined to pharmacodynamic synergy with other glucose-lowering agents and a small number of transporter-mediated effects.
Monitoring
Sitagliptin has a relatively simple monitoring profile. The two highest-yield surveillance points are renal function (because dose depends on eGFR and inappropriate dosing has been linked to AKI) and glycemic response. Class-specific surveillance for pancreatitis, hypersensitivity, arthralgia, pemphigoid, and heart-failure symptoms is symptom-driven.
-
HbA1c
Every 3 months until at goal, then every 6 months
Routine Expected reduction approximately 0.5–0.8%. If targets are not met after 3 months at maintenance dose, escalate by adding another agent rather than increasing sitagliptin dose. -
Renal Function (eGFR)
Baseline, then at least annually; sooner with intercurrent illness
Routine Mandatory before initiation. Re-dose to 50 mg if eGFR drops to 30–<45; to 25 mg if eGFR <30 or ESRD. Hold during acute illness with volume depletion. -
Self-Monitored or CGM
Patient-directed; intensified if on insulin or SU
Routine Monotherapy carries minimal hypoglycemia risk. Combination with insulin or sulfonylureas warrants more frequent monitoring during titration. -
Pancreatitis Symptoms
Each visit; immediate review if symptomatic
Trigger-based Severe persistent epigastric pain radiating to the back warrants discontinuation, lipase measurement, and imaging. Routine asymptomatic lipase screening is not recommended. -
Joint Symptoms
Each visit; review at any new arthralgia
Trigger-based Severe and disabling arthralgia is a recognized class effect (FDA Drug Safety Communication, 2015). Onset can range from days to years. Resolves on discontinuation. -
Skin / Mucosal Examination
Each visit; review with new lesions
Trigger-based Counsel patients to report new blisters, erosions, mucosal lesions, or widespread rash. Bullous pemphigoid and Stevens-Johnson syndrome warrant immediate discontinuation. -
Heart Failure Symptoms
Each visit (esp. patients with prior HF or CKD)
Trigger-based TECOS did not show increased HF risk for sitagliptin specifically, but the FDA labeling notes class concern. Investigate dyspnea, lower-extremity edema, or weight gain. -
Liver Function (LFTs)
As clinically indicated
Trigger-based Postmarketing reports of hepatic enzyme elevation. Routine screening not required; check if symptomatic. -
Body Weight
Each visit
Routine Sitagliptin is weight-neutral. Significant weight gain on therapy may indicate inadequate diabetes control or alternate drug effects (e.g., concomitant TZD or insulin). -
Lipid Panel & BP
Per CV risk management guidelines
Routine Sitagliptin has no meaningful effect on lipid profile or blood pressure. Standard CV risk surveillance still applies.
Contraindications & Cautions
An FDA Drug Safety Communication (August 2015) requires DPP-4 inhibitor labeling to warn that this class can cause severe and disabling arthralgia. Onset ranges from one day to years after starting therapy. Symptoms typically resolve upon discontinuation, and recurrence has been reported when the same or a different DPP-4 inhibitor is restarted. Clinicians should consider DPP-4 inhibitors as a possible cause of unexplained or severe joint pain and discontinue the drug if implicated.
Absolute Contraindications
- Prior serious hypersensitivity reaction to sitagliptin — anaphylaxis, angioedema, exfoliative skin reactions including Stevens-Johnson syndrome (FDA-labeled contraindication).
- Type 1 diabetes mellitus — sitagliptin is not effective for absolute insulin deficiency.
- Diabetic ketoacidosis — insulin is the cornerstone of treatment.
Relative Contraindications (Specialist Input Recommended)
- History of pancreatitis — sitagliptin has not been studied in this population per FDA labeling. Risk-benefit discussion advised; alternative classes generally preferred.
- History of severe arthralgia on another DPP-4 inhibitor — class re-challenge can precipitate symptoms; switch class if possible.
- History of bullous pemphigoid on another DPP-4 inhibitor — avoid the class.
- Pregnancy — limited human data. Insulin is the preferred therapy; use sitagliptin only if benefit clearly outweighs risk.
- Severe hepatic impairment (Child-Pugh >9) — limited clinical experience.
Use with Caution
- Risk factors for heart failure — prior HF or significant renal impairment; assess risks/benefits before initiation and monitor for HF symptoms.
- Renal impairment of any degree — verify eGFR before each prescription change. Risk of AKI increases with inappropriate dosing.
- Concomitant insulin or sulfonylureas — adjust those agents downward to mitigate hypoglycemia.
- Concomitant loop or thiazide diuretics, ACE inhibitors, ARBs, NSAIDs — additive AKI risk during volume depletion or intercurrent illness.
- Older adults with multiple comorbidities — heightened vigilance for declining renal function and hypoglycemia in combination therapy.
- Pre-procedural fasting / acute illness — temporary hold reasonable when oral intake is interrupted; resume when euvolemic.
- Breastfeeding — no human data; balance maternal benefit against unknown infant exposure.
Patient Counselling
Purpose of Therapy
Explain that sitagliptin is an oral once-daily medication that helps the body release more insulin and lower glucagon when blood sugar is high — but only when blood sugar is high — so it does not usually cause low blood sugar on its own. It typically lowers HbA1c by about 0.5–0.8 percentage points and is weight-neutral, with no expected change in body weight. It does not provide additional protection against heart attacks or kidney decline beyond what blood-sugar control offers.
How to Take
Take one tablet by mouth at the same time every day, with or without food. The tablet should be swallowed whole; do not split or crush. If a dose is missed, take it as soon as remembered the same day. If the next dose is almost due, skip the missed dose and resume the regular schedule — do not double up. Store at room temperature, away from moisture. Generic versions are widely available and therapeutically equivalent to brand-name Januvia.
Sources
- U.S. Food and Drug Administration. Januvia (sitagliptin) prescribing information. Merck Sharp & Dohme LLC; revised July 2023. dailymed.nlm.nih.gov Definitive U.S. labeling — primary source for indications, renal dosing thresholds, contraindications, adverse-reaction tables (Tables 1–3), and class-warning sections (5.1–5.7).
- European Medicines Agency. Januvia (sitagliptin) Summary of Product Characteristics. ema.europa.eu European labeling reference; useful cross-check for non-US jurisdictions including renal-function classifications.
- U.S. Food and Drug Administration. FDA Drug Safety Communication: FDA warns that DPP-4 inhibitors for type 2 diabetes may cause severe joint pain. August 28, 2015. fda.gov Source document for the class-wide arthralgia warning incorporated into all DPP-4 inhibitor labels.
- Green JB, Bethel MA, Armstrong PW, et al; TECOS Study Group. Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2015;373(3):232–242. doi.org/10.1056/NEJMoa1501352 Pivotal cardiovascular outcomes trial (n=14,671; HR 0.98, 95% CI 0.88–1.09 per-protocol for primary MACE+ endpoint) establishing CV non-inferiority and absence of HF signal for sitagliptin.
- Aschner P, Kipnes MS, Lunceford JK, et al; Sitagliptin Study 021 Group. Effect of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy on glycemic control in patients with type 2 diabetes. Diabetes Care. 2006;29(12):2632–2637. doi.org/10.2337/dc06-0703 Foundational 24-week monotherapy trial supporting initial FDA approval; placebo-subtracted HbA1c reductions of −0.79% (100 mg) and −0.94% (200 mg).
- Charbonnel B, Karasik A, Liu J, Wu M, Meininger G; Sitagliptin Study 020 Group. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing metformin therapy in patients with type 2 diabetes inadequately controlled with metformin alone. Diabetes Care. 2006;29(12):2638–2643. doi.org/10.2337/dc06-0706 24-week add-on-to-metformin trial (placebo-subtracted HbA1c reduction −0.65%) that established the most common combination regimen for sitagliptin.
- Engel SS, Round E, Golm GT, Kaufman KD, Goldstein BJ. Safety and tolerability of sitagliptin in type 2 diabetes: pooled analysis of 25 clinical studies. Diabetes Ther. 2013;4(1):119–145. doi.org/10.1007/s13300-013-0024-0 Pooled safety analysis of 25 double-blind clinical studies (14,611 patients with T2DM total, sitagliptin and comparator combined) confirming the tolerability profile observed in registration trials.
- Cornel JH, Bakris GL, Stevens SR, et al; TECOS Study Group. Effect of sitagliptin on kidney function and respective cardiovascular outcomes in type 2 diabetes: outcomes from TECOS. Diabetes Care. 2016;39(12):2304–2310. doi.org/10.2337/dc16-1415 Demonstrated that impaired kidney function predicts worse CV outcomes but sitagliptin had no clinically significant impact on cardiovascular or CKD outcomes across baseline eGFR strata.
- American Diabetes Association Professional Practice Committee. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes. Diabetes Care. Updated annually. diabetesjournals.org/care Authoritative U.S. guidance; positions DPP-4 inhibitors as third- or fourth-line agents and does not recommend combination with GLP-1 receptor agonists.
- Davies MJ, Aroda VR, Collins BS, et al. Management of hyperglycaemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2022;45(11):2753–2786. doi.org/10.2337/dci22-0034 ADA-EASD consensus shaping the relative role of DPP-4 inhibitors versus GLP-1 RAs and SGLT2 inhibitors in T2DM care pathways.
- Kidney Disease: Improving Global Outcomes (KDIGO) Diabetes Work Group. KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease. Kidney Int. 2022;102(5S):S1–S127. kdigo.org Reference for DPP-4 inhibitor selection in patients with diabetes and CKD, including the renal-dose-adjustment requirement that distinguishes sitagliptin from linagliptin.
- Drucker DJ. Mechanisms of action and therapeutic application of glucagon-like peptide-1. Cell Metab. 2018;27(4):740–756. doi.org/10.1016/j.cmet.2018.03.001 Comprehensive review of incretin biology underlying both DPP-4 inhibitor and GLP-1 receptor agonist therapy.
- Kim D, Wang L, Beconi M, et al. (2R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine: a potent, orally active dipeptidyl peptidase IV inhibitor for the treatment of type 2 diabetes. J Med Chem. 2005;48(1):141–151. doi.org/10.1021/jm0493156 Original medicinal-chemistry paper describing the discovery of sitagliptin (MK-0431; IC₅₀ = 18 nM, >1000-fold selectivity over DPP-8/9).
- Herman GA, Stevens C, Van Dyck K, et al. Pharmacokinetics and pharmacodynamics of sitagliptin, an inhibitor of dipeptidyl peptidase IV, in healthy subjects: results from two randomized, double-blind, placebo-controlled studies with single oral doses. Clin Pharmacol Ther. 2005;78(6):675–688. doi.org/10.1016/j.clpt.2005.09.002 Source for foundational PK parameters cited in the FDA PI: bioavailability ~87%, half-life 8–14 hours, ~80% renal excretion of unchanged drug, renal clearance ~388 mL/min.
- Bergman AJ, Cote J, Yi B, et al. Effect of renal insufficiency on the pharmacokinetics of sitagliptin, a dipeptidyl peptidase-4 inhibitor. Diabetes Care. 2007;30(7):1862–1864. doi.org/10.2337/dc06-2545 Foundational PK study informing renal dose-adjustment thresholds: ~2-fold AUC increase in moderate CKD and ~4-fold in severe CKD/ESRD.
- Engel SS, Suryawanshi S, Stevens SR, et al; TECOS Study Group. Safety of sitagliptin in patients with type 2 diabetes and chronic kidney disease: outcomes from TECOS. Diabetes Obes Metab. 2017;19(11):1587–1593. doi.org/10.1111/dom.12983 Confirmed acceptable safety profile of sitagliptin across renal-function strata in the TECOS population, supporting use in CKD with appropriate dose adjustment.