has no conflicts of interest to declare. Author contributions All the authors are responsible for the work described with this paper. and security of the dipeptidyl peptidase\4 inhibitor sitagliptin with the sodium\glucose transporter\2 inhibitor dapagliflozin in individuals with type 2 diabetes and slight renal insufficiency. Materials and Methods Individuals with HbA1c 7.0 to 9.5% (53 to 80?mmol/mol) and estimated glomerular filtration rate 60 to 90?mL/min/1.73m2 on metformin (1500?mg/d)??sulfonylurea were randomized to sitagliptin 100?mg ((%)Neither Hispanic nor Latino195 (63.5)194 (63.4)Hispanic or Latino109 (35.5)109 (35.6)Not reported3 (1.0)2 (0.7)Unfamiliar0 (0.0)1 (0.3)Body weight, kg87.4??20.288.7??18.0BMI, kg/m2 31.8??5.731.5??5.3HbA1c, % (mmol/mol)7.7??0.7 (60.9??7.9)7.8??0.7 (61.2??8.0)FPGa, mmol/L9.0??2.29.2??2.3eGFR, mL/min/1.73?m2 79.4??11.376.9??12.3Duration of type 2 diabetes, years10.5??7.010.7??7.4Background medicationMetformin alone212 (69.1)225 (73.5)Metformin?+?SU95 (30.9)81 (26.5) Open in a separate window Abbreviations: BMI, body mass index; FPG, fasting plasma glucose; SU, sulfonylurea. Ideals are mean??standard deviation unless otherwise noted. aTo convert to mg/dL multiply mmol/L value by 18. 3.2. Effectiveness After 24?weeks of treatment, the least squares (LS) mean change from baseline in HbA1c (95% CI) was significantly greater with sitagliptin 100?mg (?0.51% [?0.60, ?0.43] [?5.58?mmol/mol ?6.52, ?4.65]) compared with dapagliflozin (?0.36% [?0.45, ?0.27] [?3.92?mmol/mol ?4.88, ?2.95]) (Table ?(Table22 and Number ?Number2A);2A); the between\group difference was ?0.15% (?0.26, ?0.04) (?1.67?mmol/mol [?2.86, ?0.48]); (%) /th th align=”remaining” valign=”bottom” rowspan=”1″ colspan=”1″ Sitagliptin em n /em ?=?307 /th th align=”remaining” valign=”bottom” rowspan=”1″ colspan=”1″ Dapagliflozin em n /em ?=?306 /th th align=”remaining” valign=”bottom” rowspan=”1″ LRRC46 antibody colspan=”1″ Differencea /th /thead With one or moreAEs150 (48.9)158 (51.6)?2.8 (?10.1, 5.1)Drug\relatedb AEs24 (7.8)42 (13.7)?5.9 (?11.0, ?1.0)Serious AEs10 (3.3)13 (4.2)?1.0 (?4.3, 2.2)Serious drug\relatedb AEs0 (0.0)1 (0.3)?0.3Who died0 (0.0)0 (0.0)0.0Who discontinued due toAn AE10 (3.3)10 (3.3)?0.0 (?3.0, 3.0)A drug\relatedb AE5 (1.6)6 (2.0)?0.3 (?2.8, 2.0)A serious AE3 (1.0)3 (1.0)?0.0A serious drug\relatedb AE0 (0.0)1 (0.3)?0.3Patients on metformin alone( em n /em ?=?212)( em n /em ?=?225)With one or more AE of hypoglycaemia7 (3.3)8 (3.6)?0.3 (?4.0, 3.5)Symptomaticc 5 (2.4)7 (3.1)?0.8 (?4.2, 2.7)Documentedd 5 (2.4)7 (3.1)?0.8 (?4.2, 2.7)Severee 1 (0.5)2 (0.9)?0.4Asymptomaticf 2 (0.9)2 (0.9)0.1Patients on metformin and a sulfonylurea( em n /em ?=?95)( em n /em ?=?81)With one or more AE of hypoglycaemia15 (15.8)13 (16.0)?0.3 (?11.6, 10.7)Symptomaticc 13 (13.7)10 (12.3)1.3 (?9.2, 11.5)Documentedd 13 (13.7)9 (11.1)2.6 (?7.8, 12.6)Severee 0 (0.0)0 (0.0)0.0Asymptomaticf 6 (6.3)4 (4.9)1.4 (?6.5, 8.9) Open in a separate window aDifference in % vs. dapagliflozin; estimate (95% CI) was computed only for AE summary and hypoglycaemia endpoints with at least 4 individuals having events in one or more treatment organizations. bAssessed from the investigator as related to study drug. cSymptomatic hypoglycaemia: show with medical symptoms attributed to hypoglycaemia, without regard to glucose level. dDocumented symptomatic hypoglycaemia: show with medical symptoms attributed to hypoglycaemia having a recorded glucose level of 3.9 mmol/L (70?mg/dL). eSevere hypoglycaemia: show that required assistance, either medical or non\medical. Episodes having a markedly stressed out level of consciousness, a loss of consciousness, or seizure were classified as having required medical assistance, whether or not medical assistance was acquired. fAsymptomatic hypoglycaemia: finger\stick glucose ideals 3.9 mmol/L (70?mg/dL) without symptoms. The incidences of AEs and of specific AEs by system organ class (SOC) reported for 4 individuals in at least one treatment group were generally similar between the treatment organizations (Table S4). Infections and infestations was the only SOC in which the 95% CI for the between\group difference in incidence excluded 0; with this SOC the incidence of AEs was higher in the dapagliflozin group ( em n /em ?=?66 [21.6%]) than in the sitagliptin group ( em n /em ?=?46 [15.0%]), between\group difference (in %)?=??6.6 Resminostat hydrochloride [?12.7, ?0.5], in part due to a higher observed incidence of genital mycotic infections in the dapagliflozin group. The incidences of Resminostat hydrochloride specific AEs were generally similar between the sitagliptin and dapagliflozin organizations during the treatment period. The only specific AEs that occurred at a higher observed incidence in one group compared with the additional (95% CI for the between\group difference in incidence excluded 0) were abdominal pain and vomiting (higher in the sitagliptin group than in the dapagliflozin group \ abdominal pain: sitagliptin em n /em ?=?5 [1.6%], dapagliflozin em n /em ?=?0 [0.0%], difference [in %] =?1.6 [0.4, 3.8]; vomiting: sitagliptin em n /em ?=?4 [1.3%], dapagliflozin em n /em ?=?0 [0.0%], difference [in %]?=?1.3 [0.1, 3.3]) and edema peripheral (higher in the dapagliflozin group em n /em ?=?4 [1.3%] than in the sitagliptin group, em n /em ?=?0 [0.0%]; difference [in %]?=??1.3 [?3.3, ?0.1]). The incidences.Medicines. email to moc.kcrem@sseccaatad. Abstract Aim To compare the effectiveness and security of the dipeptidyl peptidase\4 inhibitor sitagliptin with the sodium\glucose transporter\2 inhibitor dapagliflozin in individuals with type 2 diabetes and slight renal insufficiency. Materials and Methods Individuals with HbA1c 7.0 to 9.5% (53 to 80?mmol/mol) and estimated glomerular filtration rate 60 to 90?mL/min/1.73m2 on metformin (1500?mg/d)??sulfonylurea were randomized to sitagliptin 100?mg ((%)Neither Hispanic nor Latino195 (63.5)194 (63.4)Hispanic or Latino109 (35.5)109 (35.6)Not reported3 (1.0)2 (0.7)Unfamiliar0 (0.0)1 (0.3)Body weight, kg87.4??20.288.7??18.0BMI, kg/m2 31.8??5.731.5??5.3HbA1c, % (mmol/mol)7.7??0.7 (60.9??7.9)7.8??0.7 (61.2??8.0)FPGa, mmol/L9.0??2.29.2??2.3eGFR, mL/min/1.73?m2 79.4??11.376.9??12.3Duration of type 2 diabetes, years10.5??7.010.7??7.4Background medicationMetformin alone212 (69.1)225 (73.5)Metformin?+?SU95 (30.9)81 (26.5) Open in a separate window Abbreviations: BMI, body mass index; FPG, fasting plasma glucose; SU, sulfonylurea. Ideals are mean??standard deviation unless otherwise noted. aTo convert to mg/dL multiply mmol/L value by 18. 3.2. Effectiveness After 24?weeks of treatment, the least squares (LS) mean change from baseline in HbA1c (95% CI) was significantly greater with sitagliptin 100?mg (?0.51% [?0.60, ?0.43] [?5.58?mmol/mol ?6.52, ?4.65]) compared with dapagliflozin (?0.36% [?0.45, ?0.27] [?3.92?mmol/mol ?4.88, ?2.95]) (Table ?(Table22 and Number ?Number2A);2A); the between\group difference was ?0.15% (?0.26, ?0.04) (?1.67?mmol/mol [?2.86, ?0.48]); (%) /th th align=”remaining” valign=”bottom” rowspan=”1″ colspan=”1″ Sitagliptin em n /em ?=?307 /th th align=”remaining” valign=”bottom” rowspan=”1″ colspan=”1″ Dapagliflozin em n /em ?=?306 /th th align=”remaining” valign=”bottom” rowspan=”1″ colspan=”1″ Differencea /th /thead With one or moreAEs150 (48.9)158 (51.6)?2.8 (?10.1, 5.1)Drug\relatedb AEs24 (7.8)42 (13.7)?5.9 (?11.0, ?1.0)Serious AEs10 (3.3)13 (4.2)?1.0 (?4.3, 2.2)Serious drug\relatedb AEs0 (0.0)1 (0.3)?0.3Who died0 (0.0)0 (0.0)0.0Who discontinued due toAn AE10 (3.3)10 (3.3)?0.0 (?3.0, 3.0)A drug\relatedb AE5 (1.6)6 (2.0)?0.3 (?2.8, 2.0)A serious AE3 (1.0)3 (1.0)?0.0A serious drug\relatedb AE0 (0.0)1 (0.3)?0.3Patients on metformin alone( em n /em ?=?212)( em n /em ?=?225)With one or more AE of hypoglycaemia7 (3.3)8 (3.6)?0.3 (?4.0, 3.5)Symptomaticc 5 (2.4)7 (3.1)?0.8 (?4.2, 2.7)Documentedd 5 (2.4)7 (3.1)?0.8 (?4.2, 2.7)Severee 1 (0.5)2 (0.9)?0.4Asymptomaticf 2 (0.9)2 (0.9)0.1Patients on metformin and a sulfonylurea( em n /em ?=?95)( em n /em ?=?81)With one or more AE of hypoglycaemia15 (15.8)13 (16.0)?0.3 (?11.6, 10.7)Symptomaticc 13 (13.7)10 (12.3)1.3 (?9.2, 11.5)Documentedd 13 (13.7)9 (11.1)2.6 (?7.8, 12.6)Severee 0 (0.0)0 (0.0)0.0Asymptomaticf 6 (6.3)4 (4.9)1.4 (?6.5, 8.9) Open in a separate window aDifference in % vs. dapagliflozin; estimate (95% CI) was computed only for AE summary and hypoglycaemia endpoints with at least 4 individuals having events in one or more treatment organizations. bAssessed from the investigator as related to study drug. cSymptomatic hypoglycaemia: show with medical symptoms attributed to hypoglycaemia, without regard to glucose level. dDocumented symptomatic hypoglycaemia: show with medical symptoms attributed to hypoglycaemia having a recorded glucose level of 3.9 mmol/L (70?mg/dL). eSevere hypoglycaemia: show that required assistance, either medical or non\medical. Episodes having a markedly stressed out level of consciousness, a loss of consciousness, or seizure were classified as having required medical assistance, whether or Resminostat hydrochloride not medical assistance was acquired. fAsymptomatic hypoglycaemia: finger\stick glucose ideals 3.9 mmol/L (70?mg/dL) without symptoms. The incidences of AEs and of specific AEs by system organ class (SOC) reported for 4 individuals in at least one treatment group had been generally similar between your treatment groupings (Desk S4). Attacks and infestations was the just SOC where the 95% CI for the between\group difference in occurrence excluded 0; within this SOC the occurrence of AEs was higher in the dapagliflozin group ( em n /em ?=?66 [21.6%]) than in the sitagliptin group ( em n /em ?=?46 [15.0%]), between\group difference (in %)?=??6.6 [?12.7, ?0.5], partly due to an increased observed occurrence of genital mycotic infections in the dapagliflozin group. The incidences of particular AEs had been generally similar between your sitagliptin and dapagliflozin groupings through the treatment period. The just particular AEs that happened at an increased observed occurrence in a single group weighed against the various other (95% CI for the between\group difference in occurrence excluded 0) had been abdominal discomfort and throwing up (higher in the sitagliptin group than in the dapagliflozin group \ abdominal discomfort: sitagliptin em n /em ?=?5 [1.6%], dapagliflozin em n /em ?=?0 [0.0%], difference [in %] =?1.6 [0.4, 3.8]; throwing up: sitagliptin em n /em ?=?4 [1.3%], dapagliflozin em n /em ?=?0 [0.0%], difference [in %]?=?1.3 [0.1, 3.3]) and edema peripheral (higher in the dapagliflozin group em n /em ?=?4 [1.3%] than in the sitagliptin group, em n /em ?=?0 [0.0%]; difference [in %]?=??1.3 [?3.3, ?0.1]). The incidences of sufferers with noted symptomatic hypoglycaemia, serious hypoglycaemia and asymptomatic hypoglycaemia had been similar between your two treatment groupings (Desk ?(Desk3).3). There have been higher incidences of sufferers with AEs of hypoglycaemia in the populace whose background medicine included an SU (15.8% and 16.0% in the sitagliptin and dapagliflozin groupings, respectively) weighed against the populace not using an SU (3.3% and 3.6% in the sitagliptin and dapagliflozin groups, respectively) (Desk ?(Desk33). There is a lower occurrence of genital mycotic an infection\related AEs in the sitagliptin group weighed against the dapagliflozin group in both guys.