Mk-0431 (Sitagliptin) API Manufacturers & Suppliers
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Sitagliptin | CAS No: 486460-32-6 | GMP-certified suppliers
A medication that supports improved glycemic control in adults with type 2 diabetes and can be incorporated into combination regimens for broader metabolic management.
Therapeutic categories
Primary indications
- Sitagliptin is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus
- It is not used to treat type 1 diabetes or patients with a history of pancreatitis
- It is also used in combination with [metformin] or [ertugliflozin]
Product Snapshot
- Oral small‑molecule DPP‑4 inhibitor supplied in multiple immediate‑ and extended‑release tablet presentations
- Used to support glycemic control in adults with type 2 diabetes, including fixed‑dose combination formats
- Approved in the US, EU, and Canada, with additional investigational listings in some regions
Clinical Overview
Sitagliptin belongs to the class of beta amino acids and derivatives. Its therapeutic effect results from selective inhibition of DPP‑4, an enzyme responsible for rapid degradation of the incretin hormones glucagon‑like peptide‑1 and glucose‑dependent insulinotropic polypeptide. By slowing incretin inactivation, sitagliptin increases circulating levels of these hormones, leading to glucose‑dependent enhancement of insulin secretion and suppression of glucagon release. The mechanism supports improved postprandial and fasting glycemic control and contributes to reductions in HbA1c.
Pharmacokinetic data indicate rapid oral absorption with minimal metabolism. Sitagliptin is a substrate of CYP3A4, CYP2C8, P‑glycoprotein, and OAT3, although renal excretion of unchanged drug is the predominant elimination pathway. Renal function has a direct impact on systemic exposure, and dose adjustments are commonly required in patients with impaired kidney function.
Safety considerations include the risk of hypoglycemia when used with insulin secretagogues, potential for angioedema, and rare events of pancreatitis. Postmarketing reports have described hypersensitivity reactions. As sitagliptin is largely renally excreted, accumulation may occur in severe renal impairment, underscoring the need for monitored dosing and appropriate patient selection.
Sitagliptin is widely available as a component of oral antidiabetic regimens, with long‑established global clinical use since its initial approval in 2006.
For API procurement, sourcing should prioritize manufacturers with demonstrated control of chiral purity, residual solvent levels, and particle size distribution. Compliance with current Good Manufacturing Practice and availability of regulatory documentation such as DMFs or CEPs supports reliable integration into finished dosage form development.
Identification & chemistry
| Generic name | Sitagliptin |
|---|---|
| Molecule type | Small molecule |
| CAS | 486460-32-6 |
| UNII | QFP0P1DV7Z |
| DrugBank ID | DB01261 |
Pharmacology
| Summary | Sitagliptin inhibits the enzyme DPP‑4, which slows degradation of the incretin hormones GLP‑1 and GIP. Sustained incretin activity enhances glucose‑dependent insulin secretion and suppresses glucagon release, supporting improved regulation of blood glucose. The drug’s primary pharmacodynamic effect is increased incretin levels with corresponding modulation of insulin and glucagon pathways via DPP‑4 blockade. |
|---|---|
| Mechanism of action | Inhibition of DPP-4 by sitagliptin slows DPP-4 mediated inactivation of incretins like GLP-1 and GIP[FDA label,A2256]. Incretins are released throughout the day and upregulated in response to meals as part of glucose homeostasis[FDA label,A2260]. Reduced inhibition of incretins increase insulin synthesis and decrease glucagon release in a manner dependant on glucose concentrations[FDA label,A2255]. These effects lead to an overall increase in blood glucose control which is demonstrated by reduced glycosylated hemoglobin (HbA1c)[FDA label,A2260]. |
| Pharmacodynamics | Sitagliptin inhibits DPP-4 which leads to increased levels of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide(GIP), decreased levels of glucagon, and a stronger insulin response to glucose[FDA label,A2260,A2255,A2256]. |
Targets
| Target | Organism | Actions |
|---|---|---|
| Dipeptidyl peptidase 4 | Humans | inhibitor |
ADME / PK
| Absorption | Sitagliptin is 87% orally bioavailable and taking it with or without food does not affect its pharmacokinetics[FDA label,A2260]. Sitagliptin reaches maximum plasma concentration in 2 hours. |
|---|---|
| Half-life | Approximately 12.4 hours[FDA label]. Other studies have reported a half life of approximately 11 hours. |
| Protein binding | 38%[FDA label,A2260]. |
| Metabolism | Sitagliptin is mostly not metabolised, with 79% of the dose excreted in the urine as the unchanged parent compound[FDA label]. Minor metabolic pathways are mediated mainly by cytochrome p450(CYP)3A4 and to a lesser extent by CYP2C8[FDA label]. After 18 hours, 81% of the dose has remained unchanged, while 2% has been N-sulfated to the M1 metabolite, 6% has been oxidatively desaturated and cyclized to the M2 metabolite, <1% glucuronidated at an unknown site to the M3 metabolite, <1% has been carbamoylated and glucuronidated to the M4 metabolite, 6% has been oxidatively saturated and cyclized to the M5 metabolite, and 2% has been hydroxylated at an unknown site to the M6 metabolite. The M2 metabolite is the cis isomer while the M5 metabolite is the trans isomer of the same metabolite. |
| Route of elimination | Approximately 79% of sitagliptin is excreted in the urine as the unchanged parent compound[FDA label]. 87% of the dose is eliminated in the urine and 13% in the feces[FDA label,A2260]. |
| Volume of distribution | 198L[FDA label,A2260]. |
| Clearance | 350mL/min[FDA label,A2256]. |
Formulation & handling
- Oral small‑molecule API suitable for conventional or film‑coated tablet formulations, with low aqueous solubility that may benefit from solubility‑enhancing excipients.
- Physicochemical stability is generally robust for solid oral dosage forms, with typical handling as a stable crystalline powder.
- Food has minimal impact on absorption, allowing flexible administration without specialized food‑dependent release design.
Regulatory status
| Lifecycle | Most Canadian and several US patents have expired, with one US patent extending exclusivity into 2027, indicating a market transitioning toward later‑stage maturity. With products already marketed in Canada, the EU, and the US, the API is moving into a period of increasing generic competition as remaining protections lapse. |
|---|
| Markets | Canada, EU, US |
|---|
Supply Chain
| Supply chain summary | Sitagliptin is supplied by multiple packagers, with the originator holding key patents in the US and Canada and serving as the primary source of the branded product. The medicine is present across major regulated markets, including the US, EU, and Canada, with various branded and repackaged presentations. Patent expiries beginning in 2023 in the US and completed in Canada suggest that generic competition is emerging or expected to accelerate as remaining protections lapse, including the 2027 US patent. |
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Safety
| Toxicity | Animal studies in pregnancy have shown no adverse effects on the mother or offspring at normal doses, however these results are not always applicable to humans. There is a voluntary fetal exposure registry [FDA label,L6067]. Animal studies at 100 times the maximum recommended human dose resulted in an increase in rib malformations. Sitagliptin is excreted in the milk of rats but it is not known if it would also be expressed in human breast milk. Because many drugs are expressed in human breast milk, the risk and benefit of prescribing the medication must be considered. There is currently a lack of safety and effectiveness data in pediatric patients. No differences in safety and efficacy were observed in geriatric patients compared to younger patients, however caution should be used in this population as they are more likely to have reduced renal function[FDA label]. Sitagliptin has also been associated with a 34% relative risk increase for all cause infection. There was no significant difference in patient response across sex, age, race, ethnicity, and BMI. |
|---|
- High‑dose animal studies (≈100× MRHD) produced skeletal malformations, indicating a potential for developmental toxicity at supratherapeutic exposure levels
- Excretion in rat milk has been observed
- Human lactational transfer is unknown, suggesting a need for defined containment and exposure‑control measures in manufacturing
Sitagliptin is a type of DPP4-Inhibitors
DPP4-Inhibitors, or dipeptidyl peptidase-4 inhibitors, belong to the subcategory of pharmaceutical active ingredients known for their therapeutic role in managing type 2 diabetes mellitus. These inhibitors work by targeting and inhibiting the action of the enzyme dipeptidyl peptidase-4 (DPP4) in the body.
DPP4 is responsible for breaking down incretin hormones, such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). By inhibiting DPP4, DPP4-Inhibitors enhance the levels and activity of these hormones. GLP-1 and GIP play crucial roles in regulating blood sugar levels by stimulating insulin release, inhibiting glucagon secretion, and slowing down gastric emptying.
The main advantage of DPP4-Inhibitors is their ability to improve glycemic control without the risk of hypoglycemia, which is a common side effect of some other diabetes medications. They are typically used as an adjunct therapy in combination with other antidiabetic agents, such as metformin, to achieve optimal glucose management.
Commonly prescribed DPP4-Inhibitors include sitagliptin, saxagliptin, linagliptin, and alogliptin. These drugs are available in oral tablet formulations, allowing for convenient administration. They have shown efficacy in lowering HbA1c levels and have a favorable safety profile.
It is important to note that DPP4-Inhibitors are not suitable for individuals with type 1 diabetes or those with a history of pancreatitis. As with any medication, there may be potential side effects, such as upper respiratory tract infections, headache, and gastrointestinal discomfort, which should be discussed with a healthcare professional.
In conclusion, DPP4-Inhibitors are a subcategory of pharmaceutical APIs that act by inhibiting the enzyme DPP4, thereby enhancing the effects of incretin hormones involved in glucose regulation. They are widely used in the management of type 2 diabetes mellitus, offering glycemic control benefits with a reduced risk of hypoglycemia.
Sitagliptin (DPP4-Inhibitors), classified under Anti-diabetics
Anti-diabetics, belonging to the pharmaceutical API (Active Pharmaceutical Ingredient) category, are a group of compounds designed to manage and treat diabetes mellitus, a chronic metabolic disorder characterized by high blood sugar levels. These medications play a vital role in controlling diabetes and preventing complications associated with the disease.
Anti-diabetics encompass a wide range of drug classes, including biguanides, sulfonylureas, thiazolidinediones, dipeptidyl peptidase-4 (DPP-4) inhibitors, sodium-glucose cotransporter-2 (SGLT2) inhibitors, and glucagon-like peptide-1 (GLP-1) receptor agonists. Each class works through different mechanisms to regulate blood sugar levels and improve insulin sensitivity.
Biguanides, such as metformin, reduce glucose production by the liver and enhance insulin sensitivity in peripheral tissues. Sulfonylureas, like glipizide, stimulate insulin secretion from pancreatic beta cells. Thiazolidinediones, including pioglitazone, improve insulin sensitivity in muscle and adipose tissues. DPP-4 inhibitors, such as sitagliptin, increase insulin release and inhibit glucagon secretion. SGLT2 inhibitors, like dapagliflozin, decrease renal glucose reabsorption, leading to increased urinary glucose excretion. GLP-1 receptor agonists, such as exenatide, enhance insulin secretion, suppress glucagon release, slow gastric emptying, and promote satiety.
These anti-diabetic APIs serve as the foundational ingredients for the formulation of various oral tablets, capsules, and injectable medications used in the treatment of diabetes. By targeting different aspects of glucose regulation, they help patients achieve and maintain optimal blood sugar levels, thus reducing the risk of diabetic complications, such as cardiovascular disease, neuropathy, and nephropathy.
It is crucial for healthcare professionals to prescribe and administer these anti-diabetic medications appropriately, considering factors like the patient's medical history, co-existing conditions, and potential drug interactions. Regular monitoring of blood glucose levels and close medical supervision are necessary to ensure effective diabetes management.
In conclusion, anti-diabetics form a critical category of pharmaceutical APIs used for the treatment of diabetes. These compounds, encompassing various drug classes, work through distinct mechanisms to regulate blood sugar levels and improve insulin sensitivity. By facilitating glucose control, anti-diabetic APIs help mitigate the risk of complications associated with diabetes mellitus, ultimately promoting better health outcomes for patients.
Sitagliptin API manufacturers & distributors
Compare qualified Sitagliptin API suppliers worldwide. We currently have 34 companies offering Sitagliptin API, with manufacturing taking place in 9 different countries. Use the table below to review supplier type, countries of origin, certifications, product portfolio and GMP audit availability.
| Supplier | Type | Country | Product origin | Certifications | Portfolio |
|---|---|---|---|---|---|
| ACE Japan | Producer | Japan | Japan | CoA | 76 products |
| Acura Labs | Producer | India | India | CoA, GMP | 18 products |
| Apino Pharma Co., Ltd. | Producer | China | China | BSE/TSE, CoA, GMP, ISO9001, MSDS, USDMF | 229 products |
| AXXO GmbH | Distributor | Germany | World | CEP, CoA, GMP, GDP, JDMF, KDMF, MSDS, USDMF | 243 products |
| Beijing Huikang Boyuan | Producer | China | China | CoA, USDMF | 10 products |
| Biocon | Producer | India | India | CoA, USDMF | 36 products |
| Divis Labs. | Producer | India | India | CoA, GMP, WC | 47 products |
| Dr. Reddy's | Producer | India | India | BSE/TSE, CoA, EDMF/ASMF, FDA, GMP, KDMF, MSDS, USDMF, WC | 170 products |
| Dr. Sahu's Laboratories | Producer | India | India | BSE/TSE, CEP, CoA, FDA, GMP, MSDS | 70 products |
| Fuxing Long Rui Pharma | Producer | China | China | CoA, USDMF, WC | 10 products |
| Global Pharma Tek | Distributor | India | India | BSE/TSE, CoA, FDA, GMP, ISO9001, MSDS | 484 products |
| HEC Pharm | Producer | Germany | China | CEP, CoA, FDA, GMP, USDMF | 31 products |
| Hikal | Producer | India | India | CoA, USDMF | 26 products |
| Honour Lab | Producer | India | India | CEP, CoA, GMP, USDMF, WC | 30 products |
| Humble Healthcaare | Producer | India | India | CoA | 30 products |
| KRKA | Producer | Slovenia | Slovenia | CoA, GMP | 81 products |
| Lupin | Producer | India | India | CoA, USDMF | 155 products |
| Moehs | Producer | Spain | Spain | CoA, USDMF | 50 products |
| Morepen Laboratories Ltd. | Producer | India | India | BSE/TSE, CEP, CoA, EDMF/ASMF, FDA, GMP, ISO9001, MSDS, USDMF, WC | 22 products |
| MSN Pharma | Producer | India | India | CoA, GMP, USDMF, WC | 31 products |
| Mylan | Producer | India | India | CoA, GMP, USDMF, WC | 201 products |
| Polpharma | Producer | Poland | Poland | BSE/TSE, CoA, FDA, GMP, MSDS, USDMF | 64 products |
| SETV Global | Producer | India | India | CoA, FDA, GMP | 515 products |
| Shaoxing Hantai Pharma | Distributor | China | China | CoA | 162 products |
| Signa | Producer | Mexico | Mexico | CoA, USDMF | 42 products |
| Sinoway industrial Co.,Lt... | Distributor | China | China | CoA, FDA, GMP, ISO9001, MSDS, USDMF | 762 products |
| Sintenovo | Producer | Spain | Spain | CoA, USDMF | 7 products |
| Solfyn International LLP | Distributor | India | China | BSE/TSE, CoA, GMP, ISO9001, MSDS, USDMF, WHO-GMP | 24 products |
| Sun Pharma | Producer | India | India | CoA, USDMF | 219 products |
| Tianjin Minxiang | Producer | China | China | CoA | 10 products |
| Torrent Pharma | Producer | India | India | CoA, USDMF | 34 products |
| Veeprho Group | Producer | Czech Republic | Czech Republic | CoA | 142 products |
| Zhejiang Apeloa Tospo-Jia... | Producer | China | China | CoA, USDMF | 15 products |
| Zhejiang Changming | Producer | China | China | CoA, USDMF | 19 products |
When sending a request, specify which Sitagliptin API quality you need: for example EP (Ph. Eur.), USP, JP, BP, or another pharmacopoeial standard, as well as the required grade (base, salt, micronised, specific purity, etc.).
Use the list above to find high-quality Sitagliptin API suppliers. For example, you can select GMP, FDA or ISO certified suppliers. Visit our help page to learn more about sourcing APIs via Pharmaoffer.
