Drug Monograph
Saxagliptin (Onglyza)
saxagliptin hydrochloride
Pharmacokinetic Profile
Half-Life
2.5 h (parent); 3.1 h (active metabolite)
Metabolism
Hepatic via CYP3A4/5
Protein Binding
Negligible
Bioavailability
~50–75% (estimated from preclinical projections)
Volume of Distribution
~2.7 L/kg (predicted)
Clinical Information
Drug Class
DPP-4 Inhibitor
Available Doses
2.5 mg, 5 mg tablets
Route
Oral, once daily
Renal Adjustment
Yes — 2.5 mg if eGFR <45
Hepatic Adjustment
Not required
Pregnancy
Insufficient data; not recommended
Lactation
Unknown if excreted in human milk
Schedule / Legal Status
Prescription only (not scheduled)
Generic Available
Yes (FDA-approved generic)
Heart Failure Signal
SAVOR-TIMI 53: HR 1.27 for HF hospitalization
Indications for Saxagliptin
| Indication | Approved Population | Therapy Type | Status |
|---|---|---|---|
| Type 2 diabetes mellitus — adjunct to diet and exercise for glycaemic control | Adults (≥18 years) | Monotherapy or combination with metformin, sulfonylurea, TZD, insulin, or SGLT2 inhibitor | FDA Approved |
Saxagliptin is approved exclusively for improving glycaemic control in adults with type 2 diabetes when used alongside lifestyle modifications. Its broad combination flexibility allows pairing with most oral antidiabetic classes as well as basal insulin. The ADA/EASD 2022 consensus algorithm positions DPP-4 inhibitors as an option when cost is a priority and SGLT2 inhibitors or GLP-1 receptor agonists are not feasible, particularly in patients without established cardiovascular disease or chronic kidney disease (ADA 2024 Standards of Care).
Off-Label Considerations
Not recommended for type 1 diabetes or diabetic ketoacidosis. Saxagliptin has no approved off-label indications with robust clinical evidence. Its use is limited to the single approved indication for T2DM glycaemic management.
Limitations of Use (FDA PI)
Saxagliptin has not been studied in patients with a history of pancreatitis. It is unknown whether patients with such history are at increased risk while using saxagliptin. Additionally, pediatric efficacy was not demonstrated in a 26-week trial of patients aged 10–17 years (NCT03199053).
Dosing of Saxagliptin
Adult Dosing by Clinical Scenario
| Clinical Scenario | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| T2DM — monotherapy when metformin is not tolerated | 5 mg once daily | 5 mg once daily | 5 mg/day | Take regardless of meals; no titration required Do not cut, crush, or chew tablets (FDA PI) |
| T2DM — add-on to metformin | 5 mg once daily | 5 mg once daily | 5 mg/day | Metformin dose unchanged Placebo-corrected A1C reduction ~0.7–0.8% |
| T2DM — add-on to sulfonylurea | 5 mg once daily | 5 mg once daily | 5 mg/day | Consider reducing SU dose to lower hypoglycaemia risk Confirmed hypo 0.8% vs 0.7% placebo (add-on to glyburide) |
| T2DM — add-on to insulin (± metformin) | 5 mg once daily | 5 mg once daily | 5 mg/day | Consider reducing insulin dose; confirmed symptomatic hypo 5.3% vs 3.3% placebo Insulin dose kept stable in pivotal trial |
| T2DM — add-on to dapagliflozin + metformin | 5 mg once daily | 5 mg once daily | 5 mg/day | Triple oral therapy Placebo-corrected A1C reduction ~0.4% |
| T2DM — concomitant strong CYP3A4/5 inhibitor | 2.5 mg once daily | 2.5 mg once daily | 2.5 mg/day | Examples: ketoconazole, itraconazole, clarithromycin, ritonavir, nelfinavir, atazanavir Ketoconazole increases saxagliptin AUC by 145% |
Renal Dose Adjustments
| Renal Function (eGFR) | Starting Dose | Maintenance Dose | Maximum Dose | Notes |
|---|---|---|---|---|
| eGFR ≥45 mL/min/1.73 m² | 5 mg once daily | 5 mg once daily | 5 mg/day | No adjustment needed |
| eGFR <45 mL/min/1.73 m² (including moderate, severe impairment, and ESRD on haemodialysis) | 2.5 mg once daily | 2.5 mg once daily | 2.5 mg/day | Administer after haemodialysis; not studied in peritoneal dialysis AUC of saxagliptin >2-fold higher in moderate-severe CKD |
Clinical Pearl: Fixed-Dose Simplicity
Unlike many antidiabetic agents, saxagliptin requires no titration. The dose is either 5 mg or 2.5 mg based solely on renal function or CYP3A4/5 inhibitor co-administration. Assess renal function before initiation and periodically thereafter. If a dose is missed, advise patients to skip it and resume the next scheduled dose rather than doubling up.
Pharmacology of Saxagliptin
Mechanism of Action
Saxagliptin is a potent, selective, and reversible inhibitor of dipeptidyl peptidase-4 (DPP-4), the enzyme responsible for degrading the incretin hormones GLP-1 and GIP shortly after their release from enteroendocrine cells following meal ingestion. By forming a slowly dissociating covalent bond with the active-site serine residue (Ser630) of DPP-4, saxagliptin extends the circulating half-life of intact incretins. This leads to a two- to three-fold rise in active GLP-1 and GIP levels, which augments glucose-dependent insulin secretion from pancreatic beta cells and suppresses glucagon release from alpha cells. The glucose-dependent nature of this mechanism confers a low intrinsic hypoglycaemia risk when saxagliptin is used without insulin or sulphonylureas. Its major metabolite, 5-hydroxy saxagliptin, retains approximately half the DPP-4 inhibitory potency of the parent compound and contributes to sustained 24-hour enzyme inhibition despite the relatively short plasma half-life of the parent drug.
ADME Profile
| Parameter | Value | Clinical Implication |
|---|---|---|
| Absorption | Tmax ~2 h (parent), ~4 h (metabolite); AUC increases ~27% with high-fat meal | Can be given with or without food; rapidly absorbed for prompt postprandial DPP-4 inhibition |
| Distribution | Vd ~2.7 L/kg (predicted in humans); protein binding negligible | Extensive extravascular distribution; disease-state protein shifts do not alter drug disposition |
| Metabolism | Primarily CYP3A4/5 to active metabolite 5-hydroxy saxagliptin (50% potency); no CYP inhibition or induction | Requires dose reduction with strong CYP3A4/5 inhibitors; low drug-drug interaction potential otherwise |
| Elimination | t½ 2.5 h (parent), 3.1 h (metabolite); renal excretion 75% of dose (24% unchanged, 36% as metabolite); faecal 22% | Dual renal-hepatic clearance; dose reduction needed at eGFR <45; removed by haemodialysis (~23% over 4 h) |
Side Effects of Saxagliptin
≥10%
Very Common (in combination with insulin or sulphonylurea)
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Hypoglycaemia (add-on to insulin) | 18.4% (vs 19.9% placebo; confirmed symptomatic: 5.3% vs 3.3%) | Driven by insulin or SU co-therapy; reduce insulin/SU dose when adding saxagliptin |
| Hypoglycaemia (add-on to glyburide) | 14.6% (vs 10.1% placebo) | Confirmed hypoglycaemia (glucose ≤50 mg/dL) was 0.8% with saxagliptin 5 mg |
1–10%
Common
| Adverse Effect | Incidence | Clinical Note |
|---|---|---|
| Upper respiratory tract infection | 7.7% (vs 7.6% placebo) | Marginal excess over placebo; no specific pattern identified |
| Urinary tract infection | 6.8% (vs 6.1% placebo) | Small absolute increase; monitor patients with recurrent UTI history |
| Headache | 6.5% (vs 5.9% placebo) | Generally mild and self-limiting; not dose-dependent |
| Peripheral oedema (with TZD co-therapy) | 8.1% (vs 4.3% placebo + TZD) | TZD-specific effect amplified by saxagliptin; monitor fluid status especially in heart failure risk patients |
| Hypoglycaemia (monotherapy) | 5.6% (vs 4.1% placebo) | Mostly mild; confirmed symptomatic events were rare without secretagogue co-therapy |
| Hypersensitivity reactions (urticaria, facial oedema) | 1.5% (vs 0.4% placebo) | Generally non-serious; one patient discontinued for generalised urticaria and facial oedema |
| Lymphocyte count decrease | 1.5% developed counts ≤750 cells/µL (5 mg; vs 0.4% placebo) | Mean decrease ~100 cells/µL from baseline; clinical significance uncertain; measure lymphocytes if prolonged infection occurs |
Serious
Serious (regardless of frequency)
| Adverse Effect | Estimated Frequency | Typical Onset | Required Action |
|---|---|---|---|
| Heart failure hospitalization | 3.5% vs 2.8% placebo (SAVOR) | Predominantly within first 12 months | Evaluate and manage per guidelines; consider discontinuation; avoid in patients with known HF risk factors |
| Acute pancreatitis | 0.2% vs 0.1% placebo (SAVOR) | Any time during therapy | Discontinue immediately; do not rechallenge; initiate supportive care |
| Anaphylaxis / angioedema | Rare (postmarketing) | Within first 3 months; some after first dose | Discontinue permanently; emergency treatment; do not rechallenge |
| Exfoliative skin conditions | Rare (postmarketing) | Variable | Discontinue; dermatology referral; alternative antidiabetic therapy |
| Bullous pemphigoid | Rare (DPP-4 class effect, postmarketing) | Months to years | Discontinue; dermatology referral for immunosuppressive treatment |
| Severe and disabling arthralgia | Rare (DPP-4 class effect, postmarketing) | 1 day to years after initiation | Consider discontinuation; symptoms resolve on drug withdrawal; may recur with rechallenge |
| Rhabdomyolysis | Very rare (postmarketing) | Variable | Check CK; discontinue; intravenous fluids; monitor renal function |
Discontinuation
Discontinuation Rates
Saxagliptin 5 mg (pooled placebo-controlled trials)
3.3% vs 1.8% placebo
Top reasons: lymphopenia (0.5%), rash (0.3%), elevated creatine phosphokinase (0.2%)
Saxagliptin 2.5 mg (pooled placebo-controlled trials)
2.2% vs 1.8% placebo
Top reasons: elevated creatinine (0.3%), rash (0.2%), lymphopenia (0.1%)
| Reason for Discontinuation | Incidence (5 mg) | Context |
|---|---|---|
| Lymphopenia | 0.5% | Dose-related effect; recurrence on rechallenge seen in some patients |
| Rash | 0.3% | Similar to placebo (0.3%); no specific pattern |
| Blood creatine phosphokinase increase | 0.2% | Investigate for rhabdomyolysis if markedly elevated with myalgia |
Managing Hypoglycaemia Risk with Combination Therapy
Saxagliptin itself carries minimal hypoglycaemia risk as monotherapy or when combined with metformin or TZDs. The primary hypoglycaemia signal arises when saxagliptin is added to insulin or sulphonylureas. In these scenarios, proactively reducing the insulin or SU dose at the time of saxagliptin initiation is prudent rather than waiting for hypoglycaemic events to occur. The SAVOR trial confirmed symptomatic hypoglycaemia was more common with saxagliptin when background therapy included insulin or an SU.
Drug Interactions with Saxagliptin
Saxagliptin is metabolised primarily by CYP3A4/5. Importantly, it does not inhibit or induce any major CYP isoenzymes and is not a significant inhibitor or inducer of P-glycoprotein. This gives saxagliptin a favourable drug interaction profile overall, with the key exceptions being strong CYP3A4/5 inhibitors and inducers.
Major
Ketoconazole (and other strong CYP3A4/5 inhibitors)
MechanismPotent CYP3A4/5 inhibition reduces saxagliptin metabolism
EffectSaxagliptin AUC increased 2.5-fold; active metabolite AUC decreased 88%
ManagementLimit saxagliptin to 2.5 mg/day; applies to ketoconazole, itraconazole, clarithromycin, ritonavir, atazanavir, nelfinavir, saquinavir, nefazodone, indinavir, telithromycin
FDA PI
Moderate
Diltiazem (moderate CYP3A4/5 inhibitor)
MechanismModerate CYP3A4/5 inhibition slows saxagliptin clearance
EffectSaxagliptin AUC increased 2.1-fold; active metabolite AUC decreased 34%
ManagementFDA PI does not mandate dose reduction; however, 2.5 mg may be considered if strong inhibitor criteria are borderline. Monitor for adverse effects
FDA PI
Moderate
Rifampicin (strong CYP3A4 inducer)
MechanismPotent CYP3A4/5 induction accelerates saxagliptin metabolism
EffectSaxagliptin AUC reduced by 76%; however, 24-hour DPP-4 inhibition was maintained
ManagementFDA PI does not specify dose increase; monitor glycaemic control. Compensatory increase in active metabolite formation preserves pharmacodynamic effect
FDA PI
Moderate
Insulin / Sulphonylureas
MechanismPharmacodynamic synergy: combined insulin-secretory and sensitising effects
EffectIncreased hypoglycaemia risk; confirmed symptomatic hypo 5.3% (with insulin) vs 3.3% placebo
ManagementConsider reducing insulin or SU dose when initiating saxagliptin; educate patient on hypoglycaemia signs
FDA PI
Minor
Metformin
MechanismNo significant pharmacokinetic interaction
EffectNo meaningful change in exposure of either drug (AUC ratio ~1.0 for both)
ManagementNo dose adjustment; safe to combine
FDA PI
Minor
Simvastatin / Digoxin / Pioglitazone / Oral Contraceptives
MechanismSaxagliptin does not inhibit or induce CYP3A4, CYP2C9, CYP2C8, or P-gp
EffectNo clinically significant changes in AUC or Cmax of co-administered drugs
ManagementNo dose adjustments needed for any of these agents
FDA PIMonitoring for Saxagliptin
-
HbA1c
Baseline, then every 3–6 months
Routine Primary efficacy measure. Target individualised per ADA guidelines (typically <7% for most adults). Expect placebo-corrected reduction of 0.5–0.8% depending on combination partner and baseline A1C. -
Renal Function (eGFR)
Before initiation, then periodically
Routine Required to determine appropriate dose (5 mg if eGFR ≥45; 2.5 mg if <45). Reassess at least annually or more frequently in patients with declining renal function. -
Heart Failure Signs
Each visit
Routine Assess for dyspnoea, orthopnoea, peripheral oedema, and rapid weight gain. SAVOR-TIMI 53 showed increased HF hospitalization risk (HR 1.27). Greatest risk in patients with prior HF history or eGFR ≤60. -
Pancreatitis Symptoms
Each visit; patient education
Routine Ask about severe persistent abdominal pain radiating to the back, with or without vomiting. Instruct patients to discontinue and seek urgent care if symptoms develop. -
Lymphocyte Count
When clinically indicated
Trigger-based Dose-related decrease in absolute lymphocyte count (~100 cells/µL at 5 mg). Check if patient develops unusual or prolonged infection. Clinical significance of decreased counts is not established. -
Skin Integrity
Each visit; patient self-monitoring
Trigger-based Watch for blisters or erosions suggestive of bullous pemphigoid (DPP-4 class effect). If suspected, discontinue and refer to dermatology. -
Joint Pain Assessment
At follow-up visits
Trigger-based Severe and disabling arthralgia is a DPP-4 class effect. Onset ranges from 1 day to years. Symptoms resolve upon discontinuation; may recur on rechallenge with same or different DPP-4 inhibitor.
Contraindications & Cautions for Saxagliptin
Absolute Contraindications
- History of serious hypersensitivity reaction to saxagliptin or any excipient in Onglyza, including anaphylaxis, angioedema, or exfoliative skin conditions (FDA PI).
- Type 1 diabetes mellitus or diabetic ketoacidosis — saxagliptin is not effective in these conditions and is not indicated for their management.
Relative Contraindications (Specialist Input Recommended)
- History of heart failure or elevated NT-proBNP — the SAVOR-TIMI 53 trial demonstrated a 27% relative increase in heart failure hospitalisation. Use only after careful risk-benefit discussion, particularly in patients with NYHA III–IV or eGFR ≤60 (FDA PI, ADA 2024).
- History of pancreatitis — it is unknown whether such patients face elevated risk; avoid if alternative options exist and discuss risk with patient.
- Prior angioedema with another DPP-4 inhibitor — cross-reactivity unknown; use with extreme caution and close monitoring.
Use with Caution
- Moderate-to-severe renal impairment (eGFR <45) — dose must be reduced to 2.5 mg daily; AUC of active moieties increases >2-fold.
- Elderly patients (≥65 years) — no specific dose adjustment required, but renal function should be assessed more frequently given age-related GFR decline.
- Concomitant use with insulin or sulphonylureas — increased hypoglycaemia risk; consider proactive dose reduction of the secretagogue or insulin.
- Concomitant strong CYP3A4/5 inhibitors — mandatory dose reduction to 2.5 mg daily.
FDA Safety Communication
Heart Failure Risk with Saxagliptin
In April 2016, the FDA added warnings to the labelling of saxagliptin-containing products regarding an increased risk of heart failure, based on findings from the SAVOR-TIMI 53 cardiovascular outcomes trial. The trial showed that 3.5% of saxagliptin-treated patients were hospitalised for heart failure compared to 2.8% on placebo (HR 1.27; 95% CI 1.07–1.51). Patients with prior heart failure or renal impairment were at highest risk. Clinicians should consider the risks and benefits before initiating saxagliptin in patients with known heart failure risk factors and monitor for symptoms during treatment.
Patient Counselling for Saxagliptin
Purpose of Therapy
Saxagliptin works alongside diet and exercise to help control blood sugar levels in type 2 diabetes. It enhances the body’s own insulin response after meals without forcing the pancreas to produce insulin when blood sugar is already low, which means it carries a low risk of causing dangerously low blood sugar on its own.
How to Take
Take one tablet once daily at the same time each day, with or without food. Do not cut, crush, or chew the tablet. If a dose is missed, skip it and take the next dose at the usual time — do not take a double dose to make up for a missed one.
Pancreatitis
Tell patient
Acute pancreatitis has been reported with this medication class. Recognise the hallmark symptom: severe, persistent pain in the upper abdomen that may radiate to the back, with or without vomiting.
Call prescriber
Stop taking saxagliptin immediately and seek urgent medical attention if this type of pain develops. Do not restart without medical advice.
Heart Failure Symptoms
Tell patient
In a large clinical trial, saxagliptin was associated with a small increase in heart failure hospitalisations. This does not mean everyone will be affected, but awareness of warning signs is important.
Call prescriber
Report increasing shortness of breath (especially when lying flat), rapid weight gain, or new/worsening ankle swelling promptly.
Hypoglycaemia Risk with Certain Combinations
Tell patient
Low blood sugar is more likely if saxagliptin is taken alongside insulin or sulphonylureas. Learn to recognise symptoms: shaking, sweating, fast heartbeat, dizziness, and hunger.
Call prescriber
Contact your healthcare team if low blood sugar episodes are frequent or severe. The insulin or sulphonylurea dose may need to be lowered.
Allergic Reactions
Tell patient
Serious allergic reactions including facial or throat swelling, skin rash, hives, and difficulty breathing have been reported, sometimes after the very first dose.
Call prescriber
Stop saxagliptin and seek emergency care immediately if swelling of face, lips, tongue, or throat occurs, or if breathing or swallowing becomes difficult.
Joint Pain
Tell patient
Some patients taking DPP-4 inhibitors have developed severe joint pain. This can start from the first day of use or develop years into therapy.
Call prescriber
Report new or worsening joint pain that is severe or limiting daily activities. The medication may need to be discontinued.
Skin Blisters
Tell patient
Rarely, DPP-4 inhibitors can cause a blistering skin condition called bullous pemphigoid. Watch for new skin blisters or areas of skin breakdown.
Call prescriber
Contact your healthcare provider promptly if you develop unexplained blisters or erosions on the skin.
Sources
Regulatory (PI / SmPC)
- AstraZeneca. ONGLYZA (saxagliptin) tablets, for oral use. Full Prescribing Information. Revised 10/2024. FDA Label Primary regulatory source for all dosing, adverse reaction incidences, pharmacokinetic data, and contraindication statements in this monograph.
- FDA Drug Safety Communication: FDA adds warnings about heart failure risk to labels of type 2 diabetes medicines containing saxagliptin and alogliptin. April 5, 2016. FDA Safety Communication Regulatory basis for the heart failure warning added to saxagliptin labelling following SAVOR-TIMI 53 results.
Key Clinical Trials
- Scirica BM, Bhatt DL, Braunwald E, et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med. 2013;369(14):1317–1326. doi:10.1056/NEJMoa1307684 Primary SAVOR-TIMI 53 publication demonstrating cardiovascular safety (non-inferiority for MACE) but increased HF hospitalization with saxagliptin.
- Scirica BM, Braunwald E, Raz I, et al. Heart failure, saxagliptin, and diabetes mellitus: observations from the SAVOR-TIMI 53 randomized trial. Circulation. 2014;130(18):1579–1588. doi:10.1161/CIRCULATIONAHA.114.010389 Detailed analysis of the heart failure signal from SAVOR-TIMI 53, identifying prior HF history, renal impairment, and elevated NT-proBNP as key risk factors.
- Udell JA, Bhatt DL, Braunwald E, et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes and moderate or severe renal impairment: observations from the SAVOR-TIMI 53 trial. Diabetes Care. 2015;38(4):696–705. doi:10.2337/dc14-1850 Subgroup analysis by renal function showing consistent HF signal irrespective of baseline eGFR and reduced progressive albuminuria with saxagliptin.
- Rosenstock J, Aguilar-Salinas C, Klein E, et al. Effect of saxagliptin monotherapy in treatment-naive patients with type 2 diabetes. Curr Med Res Opin. 2009;25(10):2401–2411. doi:10.1185/03007990903178735 Pivotal monotherapy trial demonstrating placebo-corrected A1C reductions of 0.4–0.6% with saxagliptin 2.5–5 mg.
Guidelines
- American Diabetes Association Professional Practice Committee. Standards of Care in Diabetes—2024. Diabetes Care. 2024;47(Suppl 1):S1–S321. doi:10.2337/dc24-SINT Current ADA guidelines positioning DPP-4 inhibitors as a glucose-lowering option, particularly when cost matters and cardiorenal benefit is not the primary driver of agent selection.
- 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:10.2337/dci22-0034 ADA/EASD consensus algorithm that places DPP-4 inhibitors below SGLT2i and GLP-1 RA in the treatment hierarchy when cardiorenal benefit is desired.
Mechanistic / Basic Science
- Wang A, Dorso C, Bhatt DL, et al. Potency, selectivity and prolonged binding of saxagliptin to DPP4: maintenance of DPP4 inhibition by saxagliptin in vitro and ex vivo when compared to a rapidly-dissociating DPP4 inhibitor. BMC Pharmacol. 2012;12:2. doi:10.1186/1471-2210-12-2 Demonstrates saxagliptin’s unique slow-dissociation binding kinetics from DPP-4, explaining sustained 24-hour enzyme inhibition despite a short plasma half-life.
- Augeri DJ, Robl JA, Betebenner DA, et al. Discovery and preclinical pharmacology of saxagliptin (BMS-477118): a highly potent, long-acting, orally active DPP4 inhibitor for the treatment of type 2 diabetes. J Med Chem. 2005;48(15):5025–5037. doi:10.1021/jm050261p Discovery chemistry paper describing the rational design and preclinical characterisation of saxagliptin as a substrate-like DPP-4 inhibitor.
Pharmacokinetics / Special Populations
- Boulton DW. Clinical pharmacokinetics and pharmacodynamics of saxagliptin, a dipeptidyl peptidase-4 inhibitor. Clin Pharmacokinet. 2017;56(1):11–24. doi:10.1007/s40262-016-0421-4 Comprehensive review of saxagliptin pharmacokinetics covering absorption, metabolism, renal/hepatic impairment, and drug interaction studies.
- Su H, Boulton DW, Barber N, et al. Pharmacokinetics of the dipeptidyl peptidase 4 inhibitor saxagliptin in rats, dogs, and monkeys and clinical projections. Drug Metab Dispos. 2009;37(6):1164–1171. doi:10.1124/dmd.108.026088 Preclinical pharmacokinetic study used to project human PK parameters including volume of distribution (~2.7 L/kg) and protein binding (≤30%).
- Nowicki M, Rychlik I, Haller H, et al. Long-term treatment with the dipeptidyl peptidase-4 inhibitor saxagliptin in patients with type 2 diabetes mellitus and renal impairment: a randomised controlled 52-week efficacy and safety study. Int J Clin Pract. 2011;65(12):1230–1239. doi:10.1111/j.1742-1241.2011.02812.x Key study supporting saxagliptin 2.5 mg in patients with moderate-to-severe renal impairment, demonstrating efficacy and tolerability over 52 weeks.