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metformin + sitagliptin (Januvia ER / Janumet ER / Janumet XR)

✓ Approved

Merck & Co. · DPP4 · Small Molecule

What is metformin + sitagliptin?

metformin + sitagliptin is a small molecule developed by Merck & Co.. It is approved for therapeutic indications via oral (po).

Drug Profile

Brand NamesJanuvia ER, Janumet ER, Janumet XR
CompanyMerck & Co.
Drug ClassSmall Molecule
Molecular TargetDPP4
RouteOral (PO)
StatusApproved
Sources: ClinicalTrials.gov, Merck & Co.

Mechanism of Action

Molecular Targets

metformin + sitagliptin acts on 1 molecular target:

DPP4dipeptidyl peptidase 4 (CD26, DPPIV)
Want deeper analysis?Noah AI can explain complex mechanisms and compare to similar drugs.

Therapeutic Indications

metformin + sitagliptin is developed for 1 unique indication across 1 therapeutic area.

Therapeutic AreaConditionPhase
Metabolism and nutrition disordersType 2 diabetes mellitus✓ Approved

Related Research Articles

PubMedFuture science OA2026-11-11

Distinct associations of STK11 rs2301759 and SLC29A4 rs2685753 with metformin response among Saudi patients with type 2 diabetes mellitus.

Althomali Abdullah A, Issa Noha M NM, Al-Asiri Ibrahim S IS, Algarni Misfer S MS et al.

This study investigates the genotype and allele frequencies of solute carrier family 29 member 4 (SLC29A4) rs2685753 and serine/threonine kinase 11 (STK11) rs2301759 in the Saudi population and their association with metformin response in Saudi patients with type 2 diabetes mellitus (T2DM), while comparing the findings with other ethnic populations. A prospective cohort study included 69 newly diagnosed Saudi adults with T2DM receiving metformin monotherapy for at least six months and 59 healthy controls. Genotyping was performed using TaqMan single-nucleotide polymorphism (SNP) assays. Associations between genetic variants and glycemic response were analyzed using chi-square tests and logistic regression. Among patients, 55% achieved adequate glycemic control, whereas 45% were non-responders. SLC29A4 rs2685753 showed no significant association with the metformin response. In contrast, STK11 rs2301759 demonstrated significant genotypic and allelic associations, with the C/T genotype linked to improved glycemic response. Higher baseline glycated hemoglobin (HbA1c) and family history of diabetes were associated with poorer response. STK11 rs2301759 may influence metformin efficacy in Saudi patients with T2DM and could support personalized diabetes management.

PMID 43010183
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PubMedMedicine2026-11-11

Effectiveness of metformin as initial treatment on the metabolic profile of Saudi patients newly diagnosed with type 2 diabetes mellitus: A prospective observational study.

Alkreathy Huda H, Alharbi Fawaz Abdullah FA, Magadmi Rania R, Hakami Alqassem Y AY et al.

The incidence of diabetes is increasing in several countries, including Saudi Arabia. Metformin is a common treatment for type 2 diabetes mellitus (T2DM); however, its effect on the metabolic profile of patients newly diagnosed with T2DM remains unclear. To evaluate the effects of metformin on the metabolic profile, including hemoglobin A1c (HbA1c) and lipid levels, in patients newly diagnosed with T2DM in Madinah, Saudi Arabia. This prospective observational study involved 82 participants newly diagnosed with T2DM. The participants were aged between 30 and 65 years, and their HbA1c level was ≥6.5% higher than the normal range. None of them had taken any oral hypoglycemic medication before metformin treatment. Fourteen patients did not undergo regular follow-ups. A total of 68 patients completed the study. The primary outcomes were changes in HbA1c, cholesterol, low-density lipoprotein (LDL), and hepatic enzyme marker levels. The HbA1c level significantly reduced after the 12-week treatment period (6.85% vs 7.29% at baseline, P = .001). Furthermore, 67.3% of the patients exhibited a noteworthy decrease in cholesterol (4.68 vs 5.18 mmol/L at baseline, P = .014) and LDL levels (3.03 vs 3.52 mmol/L at baseline, P = .006). However, no significant changes were observed in the levels of the other lipid profile markers. Various dosages of metformin showed comparable effects in reducing HbA1c, cholesterol, and LDL levels, but inconsistent effects on hepatic enzymes. The results suggest that metformin can be considered an initial treatment option for patients newly diagnosed with T2DM. These findings are significant given the increasing prevalence of diabetes in Saudi Arabia and the need for effective and safe treatment options. Further studies are required to explore the pharmacogenomics and metabolomics of metformin in this specific population.

PMID 43012773
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PubMedNano letters2026-11-11

ROS-Responsive Selenocysteine-Releasing Nanozyme for Targeted Ferroptosis Suppression and Pancreatic β-Cell Protection in Type 2 Diabetes.

Zhang Juncai J, Li Yuqi Y, Xie Yingying Y, Wang Runqi R et al.

Pancreatic β-cell ferroptosis, driven by oxidative stress and impaired glutathione peroxidase 4 (GPX4) activity, has emerged as an important contributor to the progression of type 2 diabetes mellitus (T2DM). However, persistent reactive oxygen species (ROS) accumulation and insufficient selenocysteine (Sec) availability limit GPX4-dependent antioxidant defense, making effective ferroptosis intervention challenging. Here, we engineered a ROS-responsive Sec-loaded copper-based single-atom nanozyme (Se@CuSAzyme) that combines catalytic ROS scavenging with Sec supplementation. Benefiting from its intrinsic superoxide dismutase- and catalase-like activities, Se@CuSAzyme efficiently eliminated excessive ROS, while oxidative stress-triggered Sec release enhanced GPX4 expression. As a result, Se@CuSAzyme markedly suppressed high glucose and erastin-induced ferroptosis, reduced lipid peroxidation, and preserved mitochondrial integrity in pancreatic β-cells. In high-fat diet/streptozotocin-induced diabetic mice, Se@CuSAzyme demonstrated therapeutic efficacy comparable to that of metformin in ameliorating hyperglycemia, alleviating insulin resistance, and increasing energy expenditure. Importantly, Se@CuSAzyme outperformed metformin in protecting against hepatic steatosis and glycolipid metabolic dysfunction.

PMID 43012594
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PubMedAlzheimer's & dementia : the journal of the Alzheimer's Association2026-11-11

Diabetes mellitus is associated with altered Alzheimer's disease pathology.

Wu Min M, Luan Ying Y, Xu Xiaowen X, Mao Xiaoxie X et al.

Diabetes mellitus (DM) is a major risk factor for dementia, yet it remains unclear whether DM accelerates cognitive decline through amyloid beta (Aβ) or tau accumulation in Alzheimer's disease (AD). In this study, we included 2784 participants from three independent observational cohorts: the Chinese Preclinical Alzheimer's Disease Study (CPAS), the Alzheimer's Disease Neuroimaging Initiative (ADNI), and Health and Aging Brain Study-Health Disparities (HABS-HD). We examined the associations of DM with Aβ positron emission tomography (PET), tau PET, plasma phosphorylated tau (p-tau)217, and longitudinal cognitive change. We also tested whether DM modified the associations of Aβ and plasma p-tau217 with subsequent tau accumulation and explored the association of metformin use with tau accumulation. We found that DM was associated with lower global Aβ burden and lower tau accumulation in CPAS and ADNI, in which cognitive impairment was more common than in HABS-HD. The associations of Aβ and plasma p-tau217 with tau accumulation were weaker among individuals with DM. In addition, DM was associated with reduced propagation of tau from early to later stage Braak regions. Longitudinal analyses in ADNI indicated that individuals with DM exhibited slower tau-related cognitive decline. In exploratory analyses, metformin use among individuals with DM was associated with lower tau accumulation compared to individuals without DM. These findings suggest that DM is associated with an attenuation of amyloid- and tau-related processes, particularly in participants with cognitive impairment, and further suggest that diabetes-related mechanisms and its management may modulate the progression of AD pathology.

PMID 43010136
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PubMedJournal of tropical medicine2026-11-11

Therapeutic Potential of Ocimum basilicum in Diabetes-Malaria Comorbidity: Evidence From Parasitemia, Biochemical, and Coagulation Outcomes in Mice.

Ayodele Opeyemi Oluwayemisi OO, Oyerinde Olawunmi Rashidat OR, Bello Oluwatosin Nancy ON, Adeigbe Daniel Gbolahan DG et al.

Diabetes-malaria comorbidity presents a significant therapeutic challenge in endemic regions, as both conditions synergistically impair hepatic and renal function and lack targeted dual-action treatments. Despite the reported antidiabetic and antiplasmodial properties of Ocimum basilicum (OCB), its efficacy in the concurrent management of these diseases remains unexplored. This study therefore evaluated the therapeutic potential of the hydromethanol extract of OCB on parasitemia, biochemical markers of organ function, inflammatory cytokines, and coagulation parameters in a murine model of diabetes-malaria comorbidity. Fifty-six male mice were divided into eight groups (n = 7): control, diabetes only, malaria only, diabetes + malaria, malaria + OCB, diabetes + OCB, diabetes + malaria + OCB, and diabetes + malaria + metformin. Diabetes was induced by streptozotocin (40 mg/kg, i.p., for 5 consecutive days), followed by inoculation with Plasmodium berghei. Parasitemia was quantified by Giemsa-stained thin blood films; fasting blood glucose (FBG), serum creatinine, urea, alanine aminotransferase (ALT), aspartate aminotransferase (AST), TNF-α, interleukin-6 (IL-6), activated partial thromboplastin time, and prothrombin time were measured. The plant extract was profiled for phytochemicals using gas chromatography-mass spectrometry (GC-MS). OCB significantly reduced parasitemia relative to untreated infected controls (p < 0.05). In comorbid animals, OCB lowered FBG by 33.22%, creatinine by 70.58%, and urea by 26.32% compared with the untreated comorbid group. Hepatic enzyme activities (ALT and AST) were reduced more effectively by OCB than by metformin, indicating hepatoprotective activity. IL-6 levels were also significantly suppressed (p < 0.01), while TNF-α and coagulation parameters remained largely unchanged. The GC-MS analysis identified forty-three bioactive compounds, with predominant compounds including gamma-sitosterol, 9,12-octadecadienoic acid, n-hexadecanoic acid, oleic acid, and N-methyl-1-adamantane acetamide. These findings demonstrate that OCB exerts antiplasmodial, antihyperglycemic, and organ-protective effects in diabetes-malaria comorbidity, highlighting its potential as a source of phytopharmaceutical agents for the integrated management of these co-occurring diseases.

PMID 43011285
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PubMedDiabetology & metabolic syndrome2026-11-11

Effects of continuous calorie restriction versus time-restricted intermittent fasting on glycemic variability in individuals with type 2 diabetes: a randomized crossover trial.

Deshmane Aditi R AR, Muley Arti S AS, Sanwalka Neha N, Deshmane Rajesh R RR

Moderate caloric restriction facilitates sustained weight control and reduces the incidence of type 2 diabetes, while meal timing and prolonged fasting may augment these advantages. Additionally, advancements in diabetes technology are improving glycemic control, by targeting Glycemic Variability (GV). However, dietary intervention studies on GV remain limited. We aimed to evaluate the changes in GV following a Continuous Calorie-restricted (CCR) Diet (reducing daily energy intake by 500 kcal/day) versus Time Restricted Intermittent Fasting (TRIF) (Calorie-matched as CCR but with restricted feeding window and only two meals) among individuals with type 2 diabetes. An interventional clinical trial with a cross-over design (CTRI/2022/07/044356) was done with 51 participants between 25 and 55 years of age, with type 2 diabetes of ≤ 5 years, taking only Metformin or drug-naive, and HbA1c between 6.5 and 8% (48-64mmol/mol). A Continuous Glucose Monitor (CGM) by Abbot was used to evaluate the Time in Range (TIR), and other GV metrics at the end of both interventions. The carry-over and treatment effects at the end of the two interventions were significantly different between the groups, with better outcomes at the end of the CCR. TIR was significantly greater following CCR (92.4 ± 5%) than following TRIF (81.4 ± 6.5%) (p = 0.001). Whereas TAR and TBR were significantly lower after CCR intervention, with a TAR of 4.6 ± 4.7% and a TBR of 2.9 ± 3.2% than after TRIF with values of 10.9 ± 8.4% and 7.7 ± 6.1% and p-value of 0.001 and 0.009, respectively. Calorie restriction is more effective in managing GV than time restricted feeding. Calorie restriction and careful planning of macro-nutrient distribution can emerge as a useful tool for planning dietary guidelines for individuals with type 2 diabetes.

PMID 43010089
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