ORIGINAL RESEARCH PAPER Volume - 9 | Issue - 7 | July - 2020 | PRINT ISSN No. 2277 - 8179 | DOI : 10.36106/ijsr INTERNATIONAL JOURNAL OF SCIENTIFIC RESEARCH STUDY OF THE EFFECT OF NEWER ANTIHYPERGLYCEMIC DRUGS TENELIGLIPTIN AND EMPAGLIFLOZINE ON GLYCEMIC LEVEL AND LIPID PROFILE IN TYPE-2 DIABETES MELLITUS PATIENTS Pharmacology Dr. Subhash PG student, Final year, Dept of Pharmacology, Darbhanga Medical College Chandra Yadav Dr. Swetabh Tutor, Pharmacology, Darbhanga Medical College *Corresponding Author, Verma* Young Scientist (DST) Institute of Post-Graduate Medical Education and Research, Dr. Debarshi Jana A.J.C. Bose Road, Kolkata-700020, West Bengal, India ABSTRACT Aim of the present study is to abserve and compare the effects of teneligliptin and Empagliozine on the glycemic level and lipid prole of the type 2 diabetes mellitus patients with an objective of providing guideline for proper selection of antihypergycemic agent in treatment of type- 2 diabetes mellitus patients. Patients with type-2 diabetes mellitus 120 individuals are selected randomly in which Group-I : 40 cases of type diabetes mellitus not on teneligliptin and Empagliozine. This will serve as control group. Group-II : 40 cases of type 2 diabetes mellitus treated with teneligliptin (DPP-4 inhibitor) 20 mg daily. This will serve as test group-I. Group-III : 40 cases of type 2 diabetes mellitus treated with Empagliozine (SGLT-2 inhibitor) 10 mg daily. This will serve as test group-2. We found that the mean HbA1c level at 12 weeks and mean HbA1c level at 24 weeks were signicantly lower in Group-III (Empagliozine) compared to Group-II (Teneligliptin) and Group-I (No Drug) which was statistically signicant. It was found that HDL was signicantly increased in Group-III (Empagliozine) compared to Group-II (Teneligliptin) and Group-I (No Drug) both 6 weeks and 12 weeks follow-up but total cholesterol was signicantly decreased in Group-II (Teneligliptin) compared toGroup-III (Empagliozine) and Group-I (No Drug). We can conclude that Empagliozine showed signicant changes in HbA1c, FBS, PPBS, HDL and triglyceride levels. Reduction in HbA1c and plasma lipids slows down the diabetes progression and decreases the risk of microvascular and macrovascular complications. KEYWORDS Antihyperglycemic Drugs, Teneligliptin , Empagliozine , Glycemic Level , Lipid Prole , Type-2 Diabetes Mellitus INTRODUCTION Aim of the present study is to abserve and compare the effects of In conjunction with lifestyle interventions, the use of metformin (MF) teneligliptin and Empagliozine on the glycemic level and lipid prole as a rst-line treatment for type 2 diabetes is well established.2 of the type 2 diabetes mellitus patients with an objective of providing However, when additional treatment is required to achieve or maintain guideline for proper selection of antihypergycemic agent in treatment glycosylated haemoglobin (HbA1c) levels at <7%, the update to a of type- 2 diabetes mellitus patients. position statement of the American Diabetes Association and the European Association for the Study of Diabetes recommends MATERIAL AND METHODS concomitant treatment with sulfonylurea (SU), a thiazolidinedione Patients with type-2 diabetes mellitus 120 individuals are selected (TZD), a dipeptidyl peptidase 4 (DPP-4) inhibitor, a sodium/glucose randomly in which :- cotransporter 2 inhibitor, a Glucagon-like peptide-1 receptor agonist or insulin.1,2 Group-I : 40 cases of type diabetes mellitus not on teneligliptin and Empagliozine. This will serve as control group. Glycaemic control is enhanced following the addition of SUs to MF, but deterioration resumes as early as 6 months. The high proportion of Group-II : 40 cases of type 2 diabetes mellitus treated with patients remaining on MF plus SU therapy despite having HbA1c ≥8% teneligliptin (DPP-4 inhibitor) 20 mg daily. This will serve as test suggests that there are signicant barriers to starting insulin or adding a group-I. third agent when treatment goals are not achieved with this combination.3 Group-III : 40 cases of type 2 diabetes mellitus treated with Empagliozine (SGLT-2 inhibitor) 10 mg daily. This will serve as test Teneligliptin has been shown to produce clinically signicant group-2. improvements in HbA1c, fasting plasma glucose (FPG) and postprandial glucose levels in patients with Type 2 Diabetes Mellitus Statistical Analysis: (T2DM), both alone and in combination with other oral anti- For statistical analysis data were entered into a Microsoft excel hyperglycaemic drugs.4-10 spreadsheet and then analyzed by SPSS (version 25.0; SPSS Inc., Chicago, IL, USA) and GraphPad Prism version 5. Two-sample t- Dipeptidyl peptidase-4 (DPP-4) inhibitors promote glucose- tests for a difference in mean involved independent samples or dependent insulin secretion and suppress glucagon secretion by unpaired samples. Unpaired proportions were compared by Chi- inhibiting the degradation of glucagon-like peptide-1 (GLP-1) and square test or Fischer's exact test, as appropriate. p-value ≤ 0.05 was glucose-dependent insulinotropic polypeptide (GIP) by binding to considered for statistically signicant. DPP-4, thereby exerting a glucose-lowering effect. 11-16 Since DPP-4 inhibitors bring a low risk of hypoglycemia, approximately 70% of RESULT AND ANALYSIS Japanese type 2 diabetes patients were prescribed the drug in 2014 In our study showed association of sex vs. group was not statistically following its launch in 2009 17-20. signicant (p=0.7906).
Sodium-glucose cotransporter-2 (SGLT2) inhibitors lower blood We found that difference of mean initial HbA1c level vs. group was glucose levels by inhibiting SGLT2 in the proximal tubule and statistically signicant (p<0.0001). Difference of mean HbA1c level at increasing glucose excretion in the urine 21. The CANVAS Program, a 12 weeks vs. group was statistically signicant (p=0.0002). We large clinical trial assessing the cardiovascular safety of the SGLT2 showed difference of mean FBS level initial vs. group was statistically inhibitor canagliozin, showed a signicant reduction of signicant (p<0.0001). Our study showed that difference of mean FBS cardiovascular events in the group administered canagliozin level at 24 weeks vs. group was statistically signicant (p<0.0001). In compared to the placebo group 22. our study we difference of mean PPBS initial vs. group was 60 International Journal of Scientific Research Volume - 9 | Issue - 7 | July - 2020 PRINT ISSN No. 2277 - 8179 | DOI : 10.36106/ijsr statistically signicant (p<0.0001). Difference of mean PPBS at 12 12 weeks vs. group was statistically signicant (p=0.0002). In our weeks vs. group was statistically signicant (p<0.0001). Difference of study we difference of mean PPBS initial vs. group was statistically mean PPBS at 24 weeks vs. group was statistically signicant signicant (p<0.0001). Difference of mean PPBS at 12 weeks vs. (p<0.0001). Difference of mean TG initial vs. group was statistically group was statistically signicant (p<0.0001). Difference of mean signicant (p=0.0002). Difference of mean TG at 6th week vs. group PPBS at 24 weeks vs. group was statistically signicant (p<0.0001). was statistically signicant (p=0.0116). Difference of mean TG at 12th Difference of mean TG initial vs. group was statistically signicant week vs. group was not statistically signicant (p=0.7384). (p=0.0002). Difference of mean TG at 6th week vs. group was statistically signicant (p=0.0116). Difference of mean TG at 12th Our study showed difference of mean LDL initial vs. group was week vs. group was not statistically signicant (p=0.7384). statistically signicant (p=0.0001). Difference of mean LDL at 6th week vs. group was statistically signicant (p=0.0431). Difference of Kumar VNet al29 (2019) found that Teneligliptin showed more mean LDL at 12th week vs. group was not statistically signicant effective reductions in HbA1c, FPG, PPBG, HDL and LDL levels. (p=0.4072). Difference of mean HDL initial vs. group was not Pioglitazone showed signicant changes in HbA1c, HDL, TC, statistically signicant (p=0.1636). triglyceride levels and signicant changes in FPG, PPBG and LDL levels. Reduction in HbA1c and plasma lipids slows down the diabetes We showed that difference of mean HDL at 6th week vs. group was progression and decreases the risk of microvascular and macrovascular statistically signicant (p=0.0057). Difference of mean HDL at 12th complications. week vs. group was statistically signicant (p<0.0001). Mahapatra Het al30 (2018) found that mean age of the sample was Our study showed that in group-I (no drug), the mean TC at 6th week 52.6 (95% CI: 51.7-53.4) years and duration of diabetes was 7.8 (6.6- (mean±s.d.) of patients was 224.7750 ± 25.5829. In group-II 8.3) years. FPG decreased from 158.8 (154.3-163.2) to 127.8 (124.5- (Teneligliptin), the mean TC at 6th week (mean±s.d.) of patients was 131.1) and PPG from 236.4 (230.7-242.0) to 191.0 (186.0-196.0) 201.3750 ± 24.2695. In Group-III (Empagliozine), the mean TC at respectively (p <0.05). 6th week (mean±s.d.) of patients was 208.7250 ± 25.2566. Difference of mean TC at 6th week vs. group was statistically signicant Singh G et al 31 (2012) found that the lipid prole of type 2 diabetics in (p=0.0002).In group-I (no drug), the mean TC at 12th week the male Punjabi population. A total of 120 Type 2 diabetic men with an (mean±s.d.) of patients was 226.2250 ± 25.8987. In group-II age range from 30 to 70 years volunteered to participate in this study. (Teneligliptin), the mean TC at 12th week (mean±s.d.) of patients was The fasting blood sugar (FBS) & lipid proles were recorded with 190.2000 ± 23.8082. In Group-III (Empagliozine), the mean TC at standard procedure. The mean age and FBS were 50.3 ± 11.8 years and 12th week (mean±s.d.) of patients was 195.9500 ± 30.0674. Difference 135.1±27.4 mg/dl respectively. There were 59% subjects with high of mean TC at 12th week vs. group was statistically signicant total cholesterol (TC) levels and 98% were having increased LDL (p<0.0001). levels. 89% of the subjects were found with lower HDL level. We showed in group-I (no drug), the mean HDL at 6th week (mean±s.d.) of DISCUSSION patients was 44.2250 ± 6.8556. In group-II (Teneligliptin), the mean Sharma SK et al 23 (2016) found that Teneligliptin has been HDL at 6th week (mean±s.d.) of patients was 47.9500 ± 5.7822. In systematically evaluated in T2DM as monotherapy with diet and Group-III (Empagliozine), the mean HDL at 6th week (mean±s.d.) of exercise and in combination with metformin, glimepiride, patients was 48.3000 ± 5.7209. Difference of mean HDL at 6th week pioglitazone, and insulin in short-term (12 weeks) and long-term (52 vs. group was statistically signicant (p=0.0057).In group-I (no drug), weeks) studies. Raghavan V et al 24 (2019) found that the mean age of the mean HDL at 12th week (mean±s.d.) of patients was 41.3250 ± patients was 50.05±12.35 years and out of the entire patient population 6.2977. In group-II (Teneligliptin), the mean HDL at 12th week 70% were males and 30% were females. At the end of 12 weeks or 3 (mean±s.d.) of patients was 50.2750 ± 4.7770. In Group-III months of metformin therapy, mean HbA1c, FBG, and PPG were (Empagliozine), the mean HDL at 12th week(mean±s.d.) of patients signicantly reduced by 0.52%, 16.2mg/dL, and 36.8mg/dL, was 50.4250 ± 5.7686. Difference of mean HDL at 12th week vs. group respectively, and 37.75% of patients achieved the HbA1c target of was statistically signicant (p<0.0001). <7%. Kim HJ et al 25 (2019) found that the mean change in HbA1c levels from baseline to week 12 was − 0.44%. At week 12, the Venkatesh SK et al 32 (2018) found that the mean value of TC, VLDL- percentage of patients achieving HbA1c<7.0% was 31.6% and that of C and LDL-C were higher in overall T2DM patients than the normal achieving HbA1c<6.5% was 11.4%, respectively. In 41.2% of range and HDL-C was lower in T2DM patients. Sultania S et al 33 patients, the HbA1c levels decreased by at least 0.5% at 12 weeks. (2017) found that There was highly signicant difference in mean Kadowaki T et al 26 (2018) found that patients showing re-elevation of HDL in diabetic patients(39.66 ± 10.17) and controls(52.02 ± 11.15) HbA1c during treatment with teneligliptin 20 mg, 89/143 (62.2%) (p<0.0001). Also a highly signicant difference was found in mean achieved HbA1c reduction after dose increase to 40 mg. triglyceride in diabetic patients (185.70 ± 76.87) and controls(125.22 ± 17.14) (p<0.0001). There was no signicant correlation found between Pattanaik SR et al 27 (2017) found that Teneligliptin similar decreases HbA1c and TC, LDL, HDL, TG. The study demonstrated the typical of HbA1c levels were observed from those of vildagliptin in either diabetic dyslipidemia which is characterized by low HDL, high high or low HOMA-R group, but no changes of HOMA-R, non-HDL- triglyceride. C levels were noted. CONCLUSION Agarwal P et al28 (2018) found that patients of the teneligliptin group We found that the mean HbA1c level at 12 weeks and mean HbA1c level showed reduced HbA1c levels. Treatment with once-daily at 24 weeks were signicantly lower in Group-III (Empagliozine) teneligliptin led to statistically signicant and clinically meaningful compared to Group-II (Teneligliptin) and Group-I (No Drug) which was reductions in HbA1c and PPG, and was well tolerated in Indian statistically signicant. patients with T2DM. We found that the mean TG level at 6 weeks and mean TG level at 12 It was found that in Group-III (Empagliozine), the mean FBS level weeks were signicantly lower in Group-III (Empagliozine) initial of patients was signicantly lower than others (p<0.0001). In compared to Group-II (Teneligliptin) and Group-I (No Drug) but LDL Group-III (Empagliozine), the mean FBS level at 12 weeks of was not signicant change in Group-III (Empagliozine) at 6 weeks patients was signicantly lower than others (p<0.0001).In Group-III and at 12 weeks follow-up. (Empagliozine), the mean FBS level at 24 weeks of patients was signicantly lower than others (p<0.0001). We can concluded that Empagliozine showed signicant changes in HbA1c, FBS, PPBS, HDL and triglyceride levels. Reduction in HbA1c We found that difference of mean initial HbA1c level vs. group was and plasma lipids slows down the diabetes progression and decreases statistically signicant (p<0.0001). Difference of mean HbA1c level at the risk of microvascular and macrovascular complications. Table: Distribution of mean all parameters in three groups. Number Mean SD Minimum Maximum Median p-value Age Group-I (No Drug) 40 56.1250 8.8526 41.0000 76.0000 56.5000 0.2501 Group-II (Teneligliptin) 40 54.1250 10.3804 42.0000 74.0000 49.5000 International Journal of Scientific Research 61 Volume - 9 | Issue - 7 | July - 2020 PRINT ISSN No. 2277 - 8179 | DOI : 10.36106/ijsr
Group-III (Empagliozine) 40 55.2500 9.4862 49.0000 78.0000 55.0000 Initial HbA1c level Group-I (No Drug) 40 7.1250 .2193 6.8000 7.6000 7.1000 <0.0001 Group-II (Teneligliptin) 40 8.3775 .3453 7.8000 9.0000 8.2500 Group-III (Empagliozine) 40 8.3895 .3861 7.6100 9.0000 8.5000 HbA1c level at 12 weeks Group-I (No Drug) 40 8.1375 .3821 7.1000 8.9000 8.1500 0.0002 Group-II (Teneligliptin) 40 8.0650 .2806 7.4000 8.7000 8.0000 Group-III (Empagliozine) 40 7.7250 .6348 6.6000 9.0000 7.8000 <0.0001 HbA1c level at 24 weeks Group-I (No Drug) 40 8.4750 .3726 7.8000 9.0000 8.6000 Group-II (Teneligliptin) 40 7.1825 .2541 6.8000 7.8000 7.1000 Group-III (Empagliozine) 40 5.9025 .4382 5.0000 6.6000 6.0000 FBS level Initial Group-I (No Drug) 40 120.5250 4.1012 115.0000 130.0000 120.0000 <0.0001 Group-II (Teneligliptin) 40 181.5000 10.5515 164.0000 200.0000 180.5000 Group-III (Empagliozine) 40 173.8250 5.9566 165.0000 190.0000 173.5000 FBS level at 12 weeks Group-I (No Drug) 40 156.6250 5.6236 148.0000 172.0000 155.0000 <0.0001 Group-II (Teneligliptin) 40 155.9250 4.6154 148.0000 168.0000 155.0000 Group-III (Empagliozine) 40 137.7000 6.0264 128.0000 152.0000 138.0000 FBS level at 24 weeks Group-I (No Drug) 40 186.0750 8.5317 174.0000 200.0000 185.0000 <0.0001 Group-II (Teneligliptin) 40 117.8750 4.5018 108.0000 130.0000 117.5000 Group-III (Empagliozine) 40 100.4750 4.6849 92.0000 111.0000 100.0000 PPBS Initial Group-I (No Drug) 40 165.2250 3.9451 156.0000 171.0000 165.0000 <0.0001 Group-II (Teneligliptin) 40 272.5000 16.9297 235.0000 295.0000 275.0000 Group-III (Empagliozine) 40 236.1500 21.0330 197.0000 260.0000 244.5000 PPBS at 12 weeks Group-I (No Drug) 40 224.9875 8.0190 214.0000 254.0000 223.0000 <0.0001 Group-II (Teneligliptin) 40 230.0225 11.0602 214.0000 254.0000 227.0000 Group-III (Empagliozine) 40 192.7000 8.8731 172.0000 203.0000 196.1500 PPBS at 24 weeks Group-I (No Drug) 40 276.5250 11.5292 252.0000 295.0000 275.0000 <0.0001 Group-II (Teneligliptin) 40 166.0250 3.2462 159.0000 171.0000 165.0000 Group-III (Empagliozine) 40 137.8000 5.3551 128.0000 150.0000 138.0000 TG Initial Group-I (No Drug) 40 118.0000 25.4074 88.0000 194.0000 111.0000 0.0002 Group-II (Teneligliptin) 40 140.9000 27.3381 93.0000 198.0000 138.5000 Group-III (Empagliozine) 40 138.5750 25.5392 93.0000 198.0000 137.0000 TG At 6th Week Group-I (No Drug) 40 120.6750 25.6059 91.0000 198.0000 114.5000 0.0116 Group-II (Teneligliptin) 40 136.9500 26.0088 90.0000 190.0000 135.0000 Group-III (Empagliozine) 40 133.5750 24.0884 90.0000 185.0000 131.5000 TG At 12th Week Group-I (No Drug) 40 123.4750 25.1681 94.0000 200.0000 116.5000 0.7384 Group-II (Teneligliptin) 40 126.5000 22.8686 82.0000 168.0000 127.0000 Group-III (Empagliozine) 40 122.4500 24.3615 82.0000 164.0000 123.0000 LDL Initial Group-I (No Drug) 40 115.8750 20.8403 83.0000 174.0000 114.0000 0.0001 Group-II (Teneligliptin) 40 135.1250 21.8787 86.0000 182.0000 138.0000 Group-III (Empagliozine) 40 134.7250 21.4846 86.0000 182.0000 138.0000 LDL At 6th Week Group-I (No Drug) 40 119.4500 21.1974 86.0000 180.0000 118.5000 0.0431 Group-II (Teneligliptin) 40 129.8250 21.3588 80.0000 170.0000 131.5000 Group-III (Empagliozine) 40 129.8250 20.6793 82.0000 175.0000 131.0000 LDL At 12th Week Group-I (No Drug) 40 121.4750 20.7117 88.0000 182.0000 121.0000 0.4072 Group-II (Teneligliptin) 40 125.1500 20.4983 75.0000 162.0000 127.0000 Group-III (Empagliozine) 40 118.9750 20.7234 80.0000 160.0000 120.5000 HDL Initial Group-I (No Drug) 40 47.9750 5.4748 35.0000 56.0000 49.5000 0.1636 Group-II (Teneligliptin) 40 45.5750 6.1723 35.0000 55.0000 44.0000 Group-III (Empagliozine) 40 46.0000 6.2429 36.0000 56.0000 45.0000 HDL At 6th Week Group-I (No Drug) 40 44.2250 6.8556 28.0000 55.0000 47.0000 0.0057 Group-II (Teneligliptin) 40 47.9500 5.7822 38.0000 57.0000 47.0000 Group-III (Empagliozine) 40 48.3000 5.7209 39.0000 57.0000 49.0000 HDL At 12th Week Group-I (No Drug) 40 41.3250 6.2977 24.0000 50.0000 43.0000 <0.0001 TC Initial Group-I (No Drug) 40 219.4500 25.4538 155.0000 256.0000 224.0000 0.8397 Group-II (Teneligliptin) 40 219.5000 23.8295 155.0000 256.0000 223.0000 Group-III (Empagliozine) 40 216.6000 25.9682 155.0000 289.0000 219.0000 TC At 6th Week Group-I (No Drug) 40 224.7750 25.5829 160.0000 271.0000 227.5000 0.0002 Group-II (Teneligliptin) 40 201.3750 24.2695 140.0000 243.0000 205.5000 Group-III (Empagliozine) 40 208.7250 25.2566 150.0000 275.0000 210.5000 TC At 12th Week Group-I (No Drug) 40 226.2250 25.8987 164.0000 266.0000 232.0000 <0.0001 Group-II (Teneligliptin) 40 190.2000 23.8082 131.0000 240.0000 192.0000 Group-III (Empagliozine) 40 195.9500 30.0674 118.0000 246.0000 204.0000 62 International Journal of Scientific Research Volume - 9 | Issue - 7 | July - 2020 PRINT ISSN No. 2277 - 8179 | DOI : 10.36106/ijsr
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