| Background: There is a high proportion of cognitive decline and a major risk of senile dementia in patients with type 2 diabetes mellitus(T2DM).The impact of current hypoglycemic drugs on cognitive ability of T2 DM is not very clear.So me experiments in animals and vitro found out that the newly developed hypoglycemic agent Glucagon-like peptide-1 analogue(GLP-1)had neuroprotective effect.Dipeptidyl peptidase-4(DPP-4)inhibitors exert the glucose-lowering effect by means of increasing the endogenous GLP-1.Whether Dipeptidyl peptidase-4 inhibitors can also affect the cognitive ability of T2 DM is not clear and definite yet.Objective: Collected randomized controlled trials about different influences of various hypoglycemic drugs on cognitive function of T2 DM to assess the impact of DPP-4 inhibitors and identify if they could improve congnitive ability and its possible related factors.Methods:Medical literature retrieval was systematically performed in three databases from January1,1976 to December31,2015.The three databases were as followed: CEN TRAL,EMBASE and MEDLINE databases.All randomized controlled trials(RCT)were about the influences on cognitive function of DPP-4 inhibitors and other hypoglycemic drugs in T2 DM.Setted up the inclusion and exclusion criteria to collect the data.Assessed the quality of included studies based on the Jadad evaluation standard.Review Manager5.5 software was used to complete the data analysis.The relative stability I2 was used to evaluate the heterogeneity of the included studies.Selected different models according to the heterogeneity(Fixed effect model or Random effects model).The DPP-4 inhibitors acted as experimental group,the other hypoglycemic drugs acted as control group.First of all,compared the Odds Ratios(OR)of cognitive impact on T2 DM between the experimental and control groups via assessing the number of congnitive decline.Secondly,used the cognitive function changes as observed object to determine whether the DPP-4 inhibitors could improve cognitive function.Finally,identified the relevant factors of DPP-4 inhibitors’ advantages on cognitive function in T2 DM via comparing glycosylated hemoglobin A1C(HBA1C),body mass index(BMI),homeostatic model assessment insulin resistance(HOMA-IR),the number of hypoglycemia.Results:1.We retrieved a total of 19 randomized controlled trials that met the selection criteria for a total of 7904 participants.4558 randomized to the experimental group,including: Vildagliptin,Sitagliptin,Saxagliptin,Alogliptin,Linagliptin.3406 randomized to the control group,including: Metformin,Sulfonylureas(glimepiride or glipizide),Insulin,Glucosidase inhibitors(acarbose or voglibose),Thiazolidinediones(TZDs)(rosiglitazone or pioglitazone).The average observed duration was 44.6±3.4 weeks.During that there were 8 randomized controlled trials using the Mini-Mental State Examination(MMSE)for a total of 3364 participants.1758 randomized to the experiental group,including: Sitagliptin,Saxagliptin,Alogliptin,Linagliptin.1606 randomized to the control group,including: Metformin,Insulin,Sulfonylureas(glipizide).2.The proportions of cognitive decline of DPP-4 inhibitors and the other hypoglycemic drugs in T2 DM were: 0.92%,2.34%;the Odds Rios(O R)of cognitive decline wer: 0.94(95%CI 0.89-0.99),25.87(95%CI 6.54-90.61)(P < 0.05).The proportions of cognitive decline of DPP-4 inhibitors subgroups in T2 DM were: Alogliptin 0.14%,Linagliptin 0.74%,Vildagliptin 0.85%,Saxagliptin 1.08%,Sitagliptin 1.33%;the ORs of corresponding subgroups were: 0.36(95%CI 0.03-0.98),0.59(95%CI0.06-0.87),0.95(95%CI0.87-0.99),1.35(95%CI 0.25-5.76),1.52(95%CI 0.34-3.58)(P<0.05).There were no significant differences between Alogliptin and Vildagliptin,Saxagliptin and Sitagliptin(P>0.05).The remaining between any two groups were significantly different(P <0.05).The proportions of cognitive decline of the other hypoglycemic drugs subgroups in T2 DM were: Insulin 1.62%,Metformin 2.10%,Glucosidase inhibitors 2.46%,TZDs 2.82%,Sulfonylureas 4.30%;the ORs of corresponding subgroups were: 0.97(95% CI 0.84-0.99),2.45(95% CI 1.01-13.45),5.43(95% CI 1.04-9.85),19.25(95% CI 3.25-70.80),35.32(95% CI 8.93-100.05)(P<0.05).There were significant differences between any two groups(P<0.05).3.The congnitive improvement means differences(MD)of DPP-4 inhibitors and the other hypoglycemic drugs in T2 DM were: 2.16(95%CI 1.23-3.50),0.81(95%CI 0.38-1.32)(P<0.05).After eliminating the studies which used Insulin,the corresponding MD were: 3.37(95%CI 1.03-5.96),0.73(95%CI 0.28-2.98)(P<0.05).4.The MDs of HBA1 C improvement of DPP-4 inhibitors and the other hypoglycemic drugs in T2 DM were: 0.53(95%CI 0.29-0.98),0.69(95%CI 0.18-0.92)(P>0.05).The MDs of BMI were: 0.28(95%CI 0.03-3.41),0.67(95%CI 0.26-2.32)(P<0.05).The MDs of HOMA-IR: 0.96(95%CI 0.01-1.55),0.67(95%CI 0.31-0.95)(P<0.05).The proportions of hypoglycemia were : 0.51%,1.00%.The ORs of hypoglycemia were: 0.33(95%CI 0.02-0.76),1.51(95%CI 1.01-3.42)(P<0.05).Conclusion: Hypoglycemic drugs Metformin,Sulfonylureas,TZDs,Glucosidase inhibitors have certain impact on the decline in cognitive function of T2 DM.Therefore,DPP-4 inhibitors and insulin could improve the cognitive ability.Alogliptin,Linagliptin,Vildagliptin are better than insulin.Alogliptin,Linagliptin performs the best.This superiority may be related to insulin resistance improvement,no increase body weight and scarce hypoglycemia. |
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