Combination Of Sitagliptin Research Articles

Chronic metabolic effects of novel gut-oriented small-molecule GPR119 agonists in diet-induced obese mice

The pharmacological activation of G-protein coupled receptor-119 (GPR119) modulates glucose, energy, and hepatic lipid homeostasis in type-2 diabetes (T2D). We developed synthetic small-molecule GPR119 agonists targeting gastrointestinal receptors. This study investigates the chronic metabolic effects of lead candidates, ps297 and ps318, individually and in combination with sitagliptin, a dipeptidyl peptidase-IV (DPP-IV) inhibitor, in high-fat diet (HFD)-induced obese (DIO) mice. In a 10-week dose-escalation protocol, DIO mice were orally treated with the investigational agents alone (10–90 mg/kg/day) and in combination with sitagliptin (20 mg/kg/day). Weekly body weight, food intake, and random blood glucose levels were monitored during the treatment phase. Post-treatment, an intraperitoneal glucose tolerance test (ipGTT), estimation of plasma biomarkers and haematological assessment were conducted. The treatment’s effect on hepatic steatosis was studied by estimating liver biomarkers and histological examinations. Ten-week sitagliptin combination therapy with the investigational entities restored incretins, insulin, and other metabolic hormonal secretions, accompanied by improved glucose homeostasis and retarded weight gain. Interestingly, monotherapy with investigational agents improved liver health by reducing liver weight, liver enzymes, and inflammation. Hepatic effects were further enhanced by co-administration of sitagliptin, evident by amelioration in hepatic steatosis endpoints such as liver weight, plasma liver enzyme concentrations, hepatic triglycerides (TG), total cholesterol (CHO), hydroxyproline content, and cytokine levels. Histopathological investigations confirmed regression in hepatic steatosis in the combination groups. These findings demonstrate the therapeutic potential of novel gut-oriented GPR119 agonists in combination with a DPP-IV inhibitor to ameliorate metabolic dysfunction-associated steatohepatitis (MASH), warranting further mechanistic investigations.

Effects of sitagliptin and L-theanine combination therapy on testicular tissue in rats with experimental diabetes

This study examines the impact of the combination of sitagliptin and L-theanine on the testis tissue of rats with experimental diabetes. Diabetes mellitus, a chronic metabolic illness, significantly reduces quality of life and can cause male infertility by decreasing sperm count, motility, and testosterone levels. Rats were allocated to five separate groups: control, diabetes, L-theanine, sitagliptin, and combination therapy. The measurements encompassed blood glucose levels, body weight, serum insulin levels, and the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). The histological examination of testicular tissue was conducted using H&E, PASH, caspase-12, and PCNA staining techniques, in addition to a TUNEL assay to detect apoptosis. Levels of oxidative stress indicators, including glutathione peroxidase (GPX), malondialdehyde (MDA), and catalase, were also evaluated. The results showed that the group of individuals with diabetes had significantly higher levels of blood glucose, apoptotic indices, GPX, catalase, and MDA levels and activities in comparison with the control group. Although both the L-theanine and sitagliptin groups exhibited some improvement, the combination therapy demonstrated the most significant decrease in histopathological damage and apoptotic markers. These results indicate that the combination of sitagliptin and L-theanine may significantly decrease testicular damage caused by diabetes, making it a promising therapeutic strategy.

The combination of sitagliptin and bee honey extract potentiates the anti-proliferative properties of 5-fluorouracil on Caco-2 cell line without detectable inflammatory events

BackgroundColon cancer originates in the colon, specifically the large intestine. It carries a poor prognosis and high mortality rate due to late diagnosis and migration. ObjectiveHere our objective was to evaluate the anticancer effects of sitagliptin (Sita) in colon cancer using Caco-2 cells. Additionally, we examined the role of bee honey extract in modulating cancer cell division and necrotic events commonly observed during drug treatments. MethodsWe monitored cell viability rate to evaluate the effect of bee honey extract compared to 5-fluorouracil (5-Fu), Sita, and their combinations. To gain further foresights into the implicated molecular interaction, we assessed the expression outline of Raf-1 and MEK, as proliferation effectors. Additionally, we examined the expression outline of p53 and Caspase 3, which are associated with programmed cell death (PCD), through western blot analysis. ResultsWe identified the Raf-1 expression pattern as a likely target for the drug combination and bee honey extract (HE), which effectively controlled colon cancer cell proliferation. Our study demonstrates that honey extract, either alone or in combination with drugs, can induce PCD by restoring the p53 and CASP-3 proteins. This was accompanied by a synergistic effect on the production of apoptotic cytokines, particularly interlukine-6 (IL-6) and IL-8, in cancer cells. Moreover, the treatment modulated the levels of pro-inflammatory cytokines, including IL-1α and IL-1β and anti-inflammatory cytokines, including IL-4 and IL-10. ConclusionOur findings shed light on honey extract and its combinations with 5-Fu and Sita in stimulating PCD and modulating cytokine production in Caco-2 cells.

Efficacy and safety of fixed dose combination of Sitagliptin, metformin, and pioglitazone in type 2 Diabetes (IMPACT study): a randomized controlled trial

BackgroundDue to the progressive decline in β-cell function, it is often necessary to utilize multiple agents with complementary mechanisms of action to address various facets and achieve glycemic control. Thus, this study aimed to evaluate the efficacy and safety of a fixed-dose combination (FDC) of metformin/sitagliptin/pioglitazone (MSP) therapy vs. metformin/sitagliptin (MS) in type 2 diabetes mellitus (T2DM).MethodsIn this phase 3, multicenter, double-blind study, patients with T2DM who exhibited inadequate glycemic control with HbA1c of 8.0–11.0% while taking ≥1500 mg/day metformin for at least 6 weeks were randomized to receive either FDC of MSP (1000/100/15 mg) or MS (1000/100 mg) per day for 24 weeks. The primary outcome measure was the change in HbA1c, and secondary outcomes included changes in fasting plasma glucose (FPG), postprandial plasma glucose (PPG), and body weight from baseline to 24 weeks along with safety and tolerability.ResultsAmong the 236 patients randomized, 207 (87.71%) successfully completed the study. All baseline characteristics were comparable between the FDC of MSP and MS groups. There was a subsequent significant reduction of HbA1c in FDC of MSP (− 1.64) vs. MS (− 1.32); between groups was [− 0.32% (95% CI, − 0.59, − 0.05)], P = 0.0208. Similar reductions were found in FPG [− 13.2 mg/dL (95% CI, − 22.86, − 3.71)], P = 0.0068, and PPG [− 20.83 mg/dL (95% CI, − 34.11, − 7.55)], P = 0.0023. There were no significant changes in body weight. A total of 27 adverse effects (AEs) and one severe AE were reported, none of which were related to the study drug.ConclusionThe FDC of MSP demonstrated significant efficacy in managing glycemic indices and could serve as a valuable tool for physicians in the management of Indian patients with T2DM.Trial registrationClinical Trials Registry of India, CTRI/2021/10/037461.

Expert opinion on fixed-dose combinations of Sitagliptin + metformin and the triple drug combination of Voglibose + Glimepiride + Metformin in the management of type 2 diabetes mellitus in Indian settings

Expert opinion on fixed-dose combinations of Sitagliptin + metformin and the triple drug combination of Voglibose + Glimepiride + Metformin in the management of type 2 diabetes mellitus in Indian settings

A Comparison of the Effects of Empagliflozin and Sitagliptin, When Combined With Metformin, on Lipid Levels in Patients with Type 2 Diabetes: A Clinical Investigation.

Introduction Type 2 diabetes (T2D) is emerging as a major global health concern. An associated condition, dyslipidemia, which acts as a significant modifiable risk factor for T2D, exhibits variations across different ethnicities and socioeconomic backgrounds. While many patients rely on metformin as their primary treatment, it does not always effectively control hyperglycemia. As a result, there is a growing need for adjunctive treatments, including sodium-glucose cotransporter-2 (SGLT2) and dipeptidyl peptidase-4 (DPP-4) inhibitors. This study evaluated the comparative effects of empagliflozin (an SGLT2 inhibitor) and sitagliptin (a DPP-4 inhibitor), both combined with metformin, on the lipid profiles of individuals with T2D. Methods Over six months at the Federal Government Polyclinic Hospital in Islamabad, we enrolled 126 participants diagnosed with T2D. Using a nonprobability consecutive sampling technique, we divided them into two groups. Group A received metformin and empagliflozin, while Group B was administered metformin and sitagliptin. We assessed their fasting lipid profiles three months into the treatment. Results Both groups consisted of 63 patients each. We observed that those in Group B, treated with sitagliptin and metformin, demonstrated a more significant reduction in total cholesterol and low-density lipoprotein-C levels than those in Group A, treated with empagliflozin and metformin. This difference proved to be statistically meaningful. Conclusion The combination of sitagliptin and metformin showed enhanced benefits in lipid profile management compared to the combination of empagliflozin and metformin in patients with T2D. This discovery underscores the need for holistic treatment modalities that factor in blood glucose levels and cardiovascular health.

Medication adjustment of afatinib and combination therapy with sitagliptin for alleviating afatinib-induced diarrhea in rats

Afatinib, as the first-line treatment for non-small cell lung cancer (NSCLC), causes severe gastrointestinal adverse reactions that greatly affect patients' quality of life and even potentially result in treatment discontinuation. Multiple dose adjustments and concomitant use of anti-diarrheal medications are commonly employed to manage diarrhea, also allowing for a recovery period between each adjustment. However, these approaches are based on empirical guidance and still have limitations. This study aims to explore reliable approaches to alleviate diarrhea by focusing on two strategies: adjusting the dosing regimen of afatinib itself and implementing combination therapy. In this study, we firstly revealed a dose-dependent relationship between afatinib-induced diarrhea and gastrointestinal epithelial damage, resulting in atrophy, reduced expression of tight junction proteins, and increased permeability. We further found that even after discontinuation of the medication, although the severity of diarrhea had improved to baseline, the tight junction proteins and permeability of the intestinal epithelium did not fully recover, and the pharmacokinetics studies showed that drug absorption significantly increased than normal. This indicated the recovery period was longer than expected and may accelerate the occurrence of subsequent episodes of diarrhea. Hence, it would be prudent to consider adjustments to the starting dose or the recovery interval. Furthermore, we initially investigated the relationship between DPP enzyme and afatinib-induced diarrhea and found a significant decrease in plasma DPP enzyme activity following afatinib-induced diarrhea. Subsequently, we conducted continuous treatment with sitagliptin and observed significant improvement in afatinib-induced diarrhea. We observed that sitagliptin can promote the production of anti-inflammatory factors, increase the expression of intestinal epithelial tight junction proteins, and improve intestinal microbiota, further validating the mechanism through the use of GLP-23-33 as GLP-2 receptor inhibitor. In conclusion, sitagliptin exhibits promising potential as a therapeutic option for managing afatinib-induced diarrhea. Taken together, our study provides valuable insights into alleviating afatinib-induced diarrhea through both afatinib medication adjustment and sitagliptin combination therapy.

Combination of spironolactone and sitagliptin improves clinical outcomes of outpatients with COVID-19: a prospective cohort study.

There are evidences showing that sitagliptin and spironolactone can potentially improve the clinical outcomes of COVID-19 cases. In this observational study on acutely symptomatic outpatient COVID-19 cases, we investigated the effects of spironolactone and sitagliptin on the outcomes of the disease. This is a prospective, naturally randomized cohort study. We followed mild to moderate symptomatic COVID-19 patients, who were treated with either combination (spironolactone 100mg daily and sitagliptin 100mg daily) or standard (steroid, antiviral and/or supportive care) therapy up to 30days. The primary outcome was hospitalization rate. The secondary outcomes included ER visit, duration of disease, and complications, such as hypoglycemia, low blood pressure or altered mental status. Of the 206 patients referred to clinics randomly, 103 received standard therapy and 103 treated with combination therapy. There were no significant differences in baseline characteristics, except for slightly higher clinical score in control group (6.92 ± 4.01 control, 4.87 ± 2.92 combination; P < 0.0001). Treatment with combination therapy was associated with lower admission rate (5.8% combination, 22.3% control; P = 0.0011), ER visits (7.8% combination, 23.3% control; P = 0.0021) and average duration of symptoms (6.67 ± 2.30days combination, 18.71 ± 6.49days control; P ≤ 0.0001). The combination of sitagliptin and spironolactone reduced duration of COVID infection and hospital visits better than standard therapeutic approaches in outpatients with COVID-19. The effects of combination of sitagliptin and spironolactone in COVID-19 patients should be further verified in a double-blind, randomized, placebo-controlled trial.

Rechallenge with a single-pill combination of sitagliptin plus extended-release metformin in patients labelled as metformin-intolerant: Mostly successful

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Pharmacokinetic comparison of sitagliptin and metformin HCl extended-release tablets versus JANUMET® XR in healthy volunteers under fasting and fed conditions.

Background and Objectives: Janumet® XR is the combination of sitagliptin and extended metformin hydrochloride produced by Merck Sharp & Dohme. It is specially designed for diabetes mellitus patients taking both drugs already. Janumet® XR exhibited clinically significant blood glucose lowering efficacy and long-term use safety. However, no generic form of Janumet® XR has been approved in western countries. The relatively high cost made the medication less prescribed. A more affordable form of this drug may benefit an immense diabetes mellitus population. The current study compared the bioequivalence (BE) of sitagliptin 100mg and metformin 1000mg produced by Nanjing Chia-Tai Tianqing Pharmaceutical Company to Janumet® XR in healthy Chinese subjects. Methods: Twenty-eight healthy Chinese subjects were enrolled in Study 1 and 2, respectively. Both studies were conducted with an open, randomized, two-period crossover design using the test (T) or the reference (R) drug. Study 1 is conducted under the fasting state, and Study 2 is under the fed state. Subjects received an oral dose of sitagliptin 100mg and metformin 1000mg, and plasma concentrations of sitagliptin and metformin were determined up to 72h post-dose. Pharmacokinetic (PK) parameters, including maximum serum concentration (Cmax) and area under the concentration-time curve up to the last quantifiable concentration (AUC0-t) of both sitagliptin and metformin, were calculated and compared between the T and R treatments. Results: In the fasting study, the geometric mean ratios of Cmax, AUC0-t, and AUC0-∞ for sitagliptin were 109.42%, 101.93%, and 101.95%, respectively; the corresponding ratios for metformin were 98.69%, 94.12%, and 93.42%, respectively. In the fed study, the geometric mean ratios of Cmax, AUC0-t, and AUC0-∞ for sitagliptin were 98.41%, 100.30%, and 100.24%, respectively; the corresponding ratios for metformin were 97.79%, 99.28%, and 100.69%, respectively. The 90% CIs of Cmax, AUC0-t, and AUC0-∞ in both studies were all within acceptance limits (80.00%-125.00%). Conclusion: The results demonstrated for the first time that sitagliptin 100mg and metformin 1000mg produced by Nanjing Chia-Tai Tianqing Pharmaceutical Company was bioequivalent to the branded Janumet® XR, and both drugs were well tolerated.

A phase I open-label clinical trial to study drug-drug interactions of Dorzagliatin and Sitagliptin in patients with type 2 diabetes and obesity

This is a phase 1, open-label, single-sequence, multiple-dose, single-center trial conducted in the US (NCT03790839), to evaluate the clinical pharmacokinetics, safety and pharmacodynamics of dorzagliatin co-administered with sitagliptin in patients with T2D and obesity. The trial has completed. 15 patients with T2D and obesity were recruited and treated with sitagliptin 100 mg QD on Day 1-5, followed by a combination of sitagliptin 100 mg QD with dorzagliatin 75 mg BID at second stage on Day 6-10 and the third stage of dorzagliatin 75 mg BID alone on Day 11-15. Primary outcomes include pharmacokinetic geometric mean ratio (GMR), safety and tolerability. Secondary outcomes include the incremental area under the curve for 4 hours post oral glucose tolerance test (iAUC) of pharmacodynamic biomarkers and glucose sensitivity. GMR for AUC0-24h and Cmax were 92.63 (90% CI, 85.61, 100.22) and 98.14 (90% CI, 83.73, 115.03) in combination/sitagliptin, and 100.34 (90% CI, 96.08, 104.79) and 102.34 (90% CI, 86.92, 120.50) in combination/dorzagliatin, respectively. Combination treatment did not increase the adverse events and well-tolerated in T2D patients. Lack of clinically meaningful pharmacokinetic interactions between dorzagliatin and sitagliptin, and an improvement of glycemic control under combination potentially support their co-administration for diabetes management.

Design expert software assisted development and evaluation of empagliflozin and sitagliptin combination tablet with improved in-vivo anti-diabetic activities

BackgroundThe combination of empagliflozin and sitagliptin to treat type-2 diabetes might be more economical and patient compliance with an additive improvement in glycemic control due to complementary modes of action. Aim of the studyTo design, formulate and optimize an immediate tablet dosage form containing empagliflozin and sitagliptin utilizing statistically reliable study design followed by in-vitro and in-vivo testing. Methodology: To determine the effects of copovidone (X1) and croscarmellose sodium (X2) amounts on the dependent variables of disintegration time and percent drug release, the formulation was developed using Design Expert Software v.13's direct compression method-based central composite design optimization study. The formulations' assay, dissolution, friability, hardness, weight variation, disintegration, and anti-diabetic effects were evaluated in comparison to the standard drug. The analysis included the use of high performance liquid chromatography (HPLC) assay methods. Mice were employed to investigate the efficacy of an anti-diabetic drug after they were administered a high-fat diet and two injections of streptozotocin at a dosage of 30 mg/kg BW each. ResultsFormulation of F3 out of nine had all in-vitro parameters at the most satisfactory condition. It was found that assay of the best formulation is 100.99% and 100.19% for empagliflozin and sitagliptin respectively. The disintegration time of F3 was found at 5.32 min. Percentage release of empagliflozin in 30 min was found 89.05% while sitagliptin was with 93.76%. The results showed that administration of F3 significantly reduced FBG (68.61%, p < 0.0001), total cholesterol levels (70.29 ± 0.48; p < 0.0001), triglycerides (70.20 ± 0.40, p < 0.0001); HDL levels (52.50 ± 0.31; p < 0.0001), LDL levels (33.34 ± 0.28; p < 0.0001), compared to diabetic control, this effect was comparable to metformin treatment. ConclusionThe direct compression approach has been used to develop, and optimize a new combination tablet incorporating empagliflozin and sitagliptin with better dissolution rate and anti-diabetic action.

A novel combination of sitagliptin and melatonin ameliorates T2D manifestations: studies on experimental diabetic models.

Type 2 diabetes (T2D) is an endocrine disorder characterized by hyperglycemia, insulin resistance, dysregulated glucose and lipid metabolism, reduced pancreatic β-cell function and mass, and a reduced incretin effect. Circadian rhythm disruption is associated with increased T2D risk. We have investigated the therapeutic potential of a combination of melatonin (M) and sitagliptin (S), a dipeptidyl peptidase IV (DPP-IV) inhibitor, in the amelioration of T2D manifestations in high-fat diet (HFD) induced T2D mouse model and also on β-cell proliferation under gluco-lipotoxicity stress in vitro. For in vivo study, mice were fed with HFD for 25weeks to induce T2D and were treated with monotherapies and S + M for four weeks. For the in vitro study, primary mouse islets were exposed to normal glucose and high glucose + palmitate to induce gluco-lipotoxic stress. Our results suggest that monotherapies and S + M improve metabolic parameters and glyco-lipid metabolism in the liver and adipose tissue, respectively, and improve mitochondrial function in the skeletal muscle. Moreover, it increases peripheral insulin sensitivity. Our in vitro and in vivo studies suggest that β-cell mass was preserved in all the drug-treated groups. The combination treatment is superior to monotherapies in the management of T2D.

Effect of Celecoxib Alone or in Combination of Sitagliptin in Monoiodoacetate Rat Model of Osteoarthritis

Background: Osteoarthritis (OA) is considered an attractive research issue; as it is the most common musculoskeletal progressive condition with no cure yet. Aims: To evaluate effect of celecoxib alone or in combination of sitagliptin in monoiodo acetate rat model of OA. Methods: A total of 40 Sprague-Dawley male rats were divided into 4 groups, negative control (n=10), positive control group (OA induced by monoiodoacetate (MIA)) (n=10), celecoxib 50mg/kg (n=10), and celecoxib 50mg/kg plus sitagliptin 20mg/kg group (n=10). Serum levels of inflammatory biomarkers and serum CTX-II were assessed for all groups. Data were analyzed statistically by SPSS version 28.00. Results: group treated with celecoxib showed a significant reduction in the inflammatory biomarkers and CTX-II serum levels compared with the OA group (P&lt;0.01). A significant reduction in CTX-II level in combination treated group relative to celecoxib treated group. Conclusion: Celecoxib imparted anti-inflammatory and cartilage protective effect in OA induced rat model. Sitagliptin combination with celecoxib added an extra cartilage protective effect by reducing cartilage degradation evident by lowering CTX-II serum levels.

Development and validation of a new spectrophotometric method for simultaneous determination of sitagliptin and metformin hydrochloride in tablet pharmaceutical dosage forms using chemometrics technique in comparison with HPLC

A new, quick, easy, affordable and eco-friendly simultaneous spectrophotometric method for determining a combined sitagliptin and metformin hydrochloride in pharmaceutical formulations was developed and validated using two chemometrics technique. These two methods are the partial least square (PLS) and principal component regression (PCR). They do not need to do a sample preparation or separation before analysis. Various drug concentrations and instrumental spectra of 25 mixed solutions of a combination of sitagliptin and metformin hydrochloride were used for model construction in the range of 200�270 nm. The R2 values of 0.9994 and 0.9996 assigned for the PLS of the sitagliptin and metformin hydrochloride and that of 0.9987 and 0.9996 for the PCR of the sitagliptin and metformin hydrochloride, respectively. It is noteworthy that these two models were successfully and effectively used with the commercial pharmaceutical formulations. Finally, the statistical comparison revealed no significant differences with the results of the HPLC reference method. The proposed method is dependable to be adopted as an alternative analytical method in the pharmaceutical industry�s quality control.

Randomized Clinical Trial on Efficacy of Empagliflozin Versus Sitagliptin, In Addition to Metformin in Type 2 Diabetic Patients.

Introduction Diabetes mellitus is a syndrome affecting more than 28.7 million people worldwide and its prevalence in Pakistan is reported to be about 11%. Management includes lifestyle changes and varied therapeutic regimens. Metformin (MET) alone and in combinations is considered as an important agent for glycemic control.Our study is based on MET combination therapy with empagliflozin versus sitagliptin in order to achieve glycemic control. Methods This randomized clinical trial was conducted in the Department of Medicine and Allied of Federal Government Polyclinic Hospital, Islamabad, from January 2022 till June 2022. The ethical approval letter numbered FGPC. 1-1/2022/Ethical Committee was taken before the commencement of the trial. The patients were divided into group A and group B. All patients were given MET 1000mg twice a day. Group A patients were additionally given sitagliptin 50mg twice daily whereas Group B patients were additionally given empagliflozin 10mg once daily. Glycemic control was documented with HbA1c at the start of treatment and after three months of treatment in both groups. A proforma was used to collect data. Analysis of the data was performed using the Statistical Package for the Social Sciences version 17 (SPSS Inc., Chicago, USA). Results A total of 126 patients were included in the study with a mean age of 53.53 ± 6.49. 81.7% were males while 18.3% were females. The mean reduction in HbA1c from baseline in group A was -0.81 ± 0.19% and in group B was -1.13 ± 0.24%with statistically significant p-value (p-value = 0.000). Conclusion Empagliflozin in combination with metformin is more efficacious in maintaining glycemic control as compared to sitagliptin in combination with metformin.

Efficacy and safety of combination of empagliflozin and metformin with combination of sitagliptin and metformin during Ramadan: an observational study

BackgroundManagement of diabetes during fasting is a clinical challenge. Sodium glucose co-transporter -2 inhibitors (SGLT2i) are considered safe with a low risk of hypoglycemia. However, studies on SGLT2i are scarce. This study was designed to compare the efficacy, safety, and tolerability of empagliflozin with metformin during Ramadan in comparison with sitagliptin and metformin.MethodsIt was a prospective, observational study, conducted at 11 different sites all across Pakistan on an outpatient basis during Ramadan (May 2021–June 2021). including 132 patients, 88 who received metformin and sitagliptin, and 44 patients who received metformin and empagliflozin.ResultsPatients of the SGLT-2i group experienced similar symptomatic hypoglycemic episodes (15.9%) as the sitagliptin group. There was an improvement in blood sugar levels after the use of SGLT-2i (RBS 181 ± 64 before Ramadan vs 162 ± 53 after Ramadan). HbA1c also improved after the use of SGLT-2i before and after Ramadan (7.2 ± 0.8 vs 6.9 ± 0.9 for Metformin + Empagliflozin and 7.8 ± 1.5 vs 7.6 ± 1.6 for Metformin and sitagliptin). Weight and BMI improved after the use of SGLT-2i (BMI 36.5 ± 4.8 before Ramadan and 33.7 ± 2.4 after Ramadan). There were no reported cases of urinary tract infection in the empagliflozin group.ConclusionSGLT-2 inhibitors combined with metformin for patients with diabetes during Ramadan fasting is as effective, safe and well tolerated as DPP4 combined with metformin.

Sitagliptin Potentiates the Anti-Neoplastic Activity of Doxorubicin in Experimentally-Induced Mammary Adenocarcinoma in Mice: Implication of Oxidative Stress, Inflammation, Angiogenesis, and Apoptosis

Sitagliptin (STG) is a highly selective dipeptidyl peptidase-4 inhibitor recently used in the treatment of type 2 diabetes. The current study aimed to investigate the anti-neoplastic effect of STG alone and in combination with Doxorubicin (Dox), a known chemotherapeutic agent but with ominous side effects. After intramuscular inoculation of 2 × 106 Ehrlich tumor cells, Female Swiss mice were divided into tumor-bearing control, STG-treated, Dox-treated, and a combination of STG and Dox-treated groups. The results showed a significant reduction in the tumor growth of the treated animals in comparison with those of the positive control group with a more prominent effect in the co-treated group. Where, the anti-proliferative and apoptotic effect of STG, and its chemo-sensitizing ability, when used in combination with Dox, was mediated by modulation of oxidative stress (MDA and GSH), attenuation of tumor inflammation (IL-6 and IL-1β), and angiogenesis (VEGF), suppressing proliferation (β-catenin and cyclin-D1) and enhancement of apoptosis (survivin, p53, caspase 3). Thus, in conclusion, STG as adjunctive therapy for Dox could be a strategy for the treatment of breast cancer patients, by their ability in hindering cell proliferation and minimizing the associated oxidative and inflammatory adverse reactions.

Comparative study to evaluate safety and efficacy of Metformin versus sitagliptin alone and combination in type 2 diabetes mellitus

Type 2 Diabetes mellitus (Type 2DM) is chronic, lifelong progressive metabolic disease characterized by hyperglycaemia due to absolute or relative insulinopaenia. The metabolic dysregulation that contributes to hyperglycaemia includes diminished insulin secretion, impaired glucose utilization or increased glucose production, and eventually causes pathophysiological changes in multiple organs and organ systems. Our study showed Sitagliptin was superior in reducing HOMA-IR when compared with metformin. If combination of Sitagliptin and metformin is used far superior reduction will be achieved on HOMA- IR. Limitation of our study was short duration of study and small sample size.

Relationships Between the Achieved Target Levels of LDL Cholesterol and the State of Various Types of LV EF in Patients with Coronary Artery Disease and Type 2 Diabetes

Today, diabetes mellitus is one of the most powerful risk factors for the development of cardiovascular diseases and its complications. [1] In 50% of patients with type 1 diabetes and in 80% of people with type 2 diabetes, early disability and premature death are recorded due to cardiovascular complications. People with diabetes are often at risk for strokes, heart attacks, and high blood pressure. In this regard, the main strategy for the treatment of patients with diabetes is to prevent the development of cardiovascular complications, which includes strict control of glycemia, blood pressure, as well as antiplatelet and lipid-lowering therapy. Despite the fact that strict glycemic control alone does not reduce the risk of myocardial infarction and mortality from it, most epidemiological and pathophysiological studies indicate a worse prognosis and a higher incidence of cardiovascular complications in chronic hyperglycemia. The use of a fixed combination of sitagliptin / metformin is one of the preferred options in the treatment of type 2 diabetes in patients with a high risk of cardiovascular disease due to the presence of type 4 dipeptidyl peptidase inhibitors of cardio protective effects. In this paper, changes in the lipid spectrum in patients with ischemic heart disease and type 2 diabetes mellitus with varying degrees of cardiac output are related to the number of years the patient has had diabetes mellitus, sitagliptin / metformin and statin drugs changes depending on the dose are highlighted.