Table 2

- Studies that evaluated the effects of different antidiabetic drugs on the serum level of uric acid in patients with type-2 diabetes.

Drug classificationReferencesStudy locationStudy designPatients (N)Age (years)Gender (M/F)
Metformin* (-)Gregorio et al20ItalyBefore-after study7676.44±1.0331/45
Gliclazide (sulfonylurea)Kilo et al30USABefore-after study2956.119/10
Suijk et al32NetherlandsRandomized, double-blind, comparator-controlled, intervention trial44 (gliclazide, n=20; dapagliflozin, n=24)65 (8)17/3
Glimepiride (suilfonylurea)Kitazawa et al33JapanMulticenter, randomized, open-label, parallel-group trial64 (glimepiride, n=31; tofogliflozin, n=33)57.6±9.319/12
Sitagliptin (DDP4i)Matsushima et al34JapanMulticenter, randomized, open-label, parallel-group trial241 (sitagliptin, n=120; voglibose, n=121)63.2±13.872/48
Kutoh et al35JapanProspective, nonrandomized, observational study6456.0±12.350/14
Tojikubo et al36JapanBefore-after study7366±1341/32
Fuchigami et al37JapanProspective, randomized, open-label, blinded-endpoint, parallel-group trial331 (sitagliptin, n=163; dapagliflozin, n=168)57.9±12.195/68
Alogliptin (DDP4i)Kutoh et al35JapanProspective, nonrandomized, observational study5552.4±13.246/9
Linagliptin* (DDP4i)Tojikubo et al36JapanBefore-after study7366±1341/32
Yamagishi et al38JapanProspective trial2669.4±12.418/8
Vildagliptin* (DDP4i)Shimodaira et al39JapanRetrospective study6267.2±12.242/20
Voglibose (alpha-glucosidase inhibitor)Matsushima et al34JapanMulticenter, randomized, open-label, parallel-group trial241 (voglibose, n=121; sitagliptin, n=120)63.2±11.671/50
Troglitazone* (thiazolidinedione)Iwatani et al42JapanBefore-after study9561.1±10.361/34
Rosiglitazone* (thiazolidinedione)Seber et al43TurkeyProspective trial40NRNR
Macić-Dzanković et al44SarajevoBefore-after study21NRNR
Pioglitazone* (thiazolidinedione)Kutoh et al45JapanCohort study1953.6±12.6NR
Insulin (-)MacFarlane et al47USAMatched cohort study2357 (47,64)11/12
Exenatide (GLP-1 RA)Dutour et al51FranceProspective randomized clinical trial44 (exenatide, n=22; reference, n=22)51±213/9
Muskiet et al52Sweden, Finland, NetherlandsPost-hoc analysis of a randomized, open-label, active-comparator, parallel-group trial54 (exenatide, n=26; insulin glargine, n=28)59.7±8.116/10
Liraglutide (GLP-1 RA)Tonneijck et al53NetherlandsRandomized, double-blind, placebo-controlled trial36 (liraglutide, n=19; placebo, n=17)63.0±7.027/9
Nakaguchi et al54JapanOpen-label, parallel-group, randomized controlled trial61 (liraglutide, n=30; empagliflozin, n=31)67.2±9.021/9
Kurir et al55CroatiaNon-randomized, controlled, interventional study1560 (55,68)all male
Liakos et al56GreeceRandomized, double blind, placebo-controlled trial62 (liraglutide, n=31; placebo, n=31)60.5±12.019/12
Lixisenatide (GLP-1 RA)Tonneijck et al53NetherlandsRandomized, open-label, comparator-controlled trial35 (lixisenatide, n=17; insulin glulisine, n=18)61.7±6.623/12
Dulaglutide (GLP-1 RA)Kuchay et al57IndiaOpen-label, parallel-group, randomized controlled trial64 (dulaglutide,n=32; control,n=32)46.6±9.123/9
Hirai et al58JapanRetrospective comparative study20 (dulaglutide, n=10; liraglutide, n=10)67.6±9.96/4
Iwasaki et al59JapanSingle–center, open–label, single–arm, pilot study3666.7±11.115/21
Empagliflozin* (SGLT2i)You Y et al61NAMeta-analysis780151–78.4NR
Dapagliflozin* (SGLT2i)Hao Z et al62ChinaRandomized controlled trial59 (dapagliflozin, n=29; control,n=30)57.77±12.2920/9
Fuchigami et al37JapanProspective, randomized, open-label, blinded-endpoint, parallel-group trial331 (dapagliflozin, n=168; sitagliptin, n=163)58.3±12.4104/64
Suijk et al32NetherlandsRandomized, double-blind, comparator-controlled intervention trial44 (dapagliflozin, n=24; gliclazide, n=20)63±717/7
Canagliflozin* (SGLT2i)Davies et al63NRPost-hoc analysis of pooled data from four randomized placebo-controlled phase III multinational studies2313 (canagliflozin, n=1667; placebo, n=646)59.1±9.6812/855
Luseogliflozin* (SGLT2i)Seino et al64JapanPhase II, randomized, placebo-controlled, double-blind, parallel-group study236 (luseogliflozin,n=182; placebo,n=54)58.3±9.435/26
Chino et al65JapanRetrospective study480 (luseogliflozin, n=297; placebo, n=183)58±10207/90
Tofogliflozin* (SGLT2i)Terauchi et al66JapanRandomized, double-blind, placebo-controlled multicentre trial211 (tofogliflozin, n=141; placebo, n=70)59.1±10.890/51
Ipragliflozin* (SGLT2i)Tanaka et al67JapanRandomized, open-label, active-controlled, blinded-endpoint trial30 (ipragliflozin,n=15; control,n=15)59.1±11.28/7
Tsukagoshi-Yamaguchi et al68JapanProspective, multicenter, open-label, blinded-end point, randomized, controlled study30 (ipragliflozin,n=15; metformin,n=15)57.8±13.39/6
Nagao et al69JapanMulticenter, open-label, randomized controlled trial160 (ipragliflozin,n=77; sitagliptin,n=83)62(53–67)44/33
Drug classificationReferencesStudy locationBMI (kg/m2)eGFR (mL/min/1.73 m2)Baseline Serum UA (mg/dL)HbA1c (%)Duration of diabetes (years)
Metformin* (-)Gregorio et al20ItalyNRNR5.88±0.25>915.08±1.27
Gliclazide (Sulfonylurea)Kilo et al30USA42.8% overweightNRNR10.1±0.448.03
Suijk et al32Netherlands32±489 (22)5.2±0.97.4±0.6NR
Glimepiride (Suilfonylurea)Kitazawa et al33Japan25.4±3.888.5±16.25.5±1.67.5±0.47.7±6.7
Sitagliptin (DDP4i)Matsushima et al34Japan25.0±4.588.0±23.35.08±1.147.9±1.0NR
Kutoh et al35Japan24.58±4.35NR4.91±1.2810.14±2.19NR
Tojikubo et al36Japan24.6±5.078.0±24.45.10±1.138.19±1.0715.3±7.8
Fuchigami et al37Japan27.9±4.278.9±16.95.4±1.47.8±0.85.6±5.8
Alogliptin (DDP4i)Kutoh et al35Japan25.69±5.21NR4.69±1.6010.60±2.24NR
Linagliptin* (DDP4i)Tojikubo et al36Japan24.6±4.171.8±23.35.63±1.247.32±1.0515.3±7.8
Yamagishi et al38Japan24.7±3.6NR5.5±1.27.4±1.4NR
Vildagliptin* (DDP4i)Shimodaira et al39Japan24.7±3.871.7±26.86.0±1.67.7±1.0NR
Voglibose (alpha-glucosidase inhibitor)Matsushima et al34Japan25.1±4.583.7±22.25.13±1.407.8±0.8NR
Troglitazone* (Thiazolidinedione)Iwatani et al42Japan25.4±3.0NR5.5±1.28.4±1.3NR
Rosiglitazone* (Thiazolidinedione)Seber et al43Turkey30.31±5.3NR4.78±1.19.95±9.7NR
Macić-Dzanković et al44SarajevoNRNR6.22±1.318.55±1.9NR
Pioglitazone* (Thiazolidinedione)Kutoh et al45Japan27.82±6.32NR6.87±0.738.63±1.74Newly Diagnosed
Insulin (-)MacFarlane et al47USA38.1 (32.8,39.1)NR6.4 (4.6, 8.2)8.9 (7.5, 10.9)NR
Exenatide (GLP-1 RA)Dutour et al51France37.2±1.8NR6.3±1.5NR4 (2, 8)
Muskiet et al52Sweden, Finland, Netherlands30.4±4.184.7±17.0NR7.53±0.98NR
Liraglutide (GLP-1 RA)Tonneijck et al53Netherlands31.2 (29.2,33.3)79±35.39±1.077.4±0.78 (4–12)
Nakaguchi et al54Japan26.4±4.663.3±18.95.3±1.38.04±0.7518.8±9.9
Kurir et al55Croatia40.9±7.3NR6.69±1.217.98±0.70NR
Liakos et al56Greece33.6 (7.9)82.3 (30.3)NR7.8 (1.7)8.0 (6.0)
Lixisenatide (GLP-1 RA)Tonneijck et al53Netherlands31.5±4.093±35.68±1.198.0±0.913±7
Dulaglutide (GLP-1 RA)Kuchay et al57India29.6±3.6NR5.0±1.78.4±1.04.9±3.1
Hirai et al58Japan25.7±3.220.3±10.46.3±0.87.2±0.8NR
Iwasaki et al59Japan28.7±5.3NR4.93±1.357.80±0.9917.9±9.1
Empagliflozin* (SGLT2i)You Y et al61NANRNRNRNRNR
Dapagliflozin* (SGLT2i)Hao Z et al62China27.34±3.88NR5.86±1.729.89±1.2412.20±6.59
Fuchigami et al37Japan27.8±4.079.0±18.55.4±1.37.8±0.86.0±6.4
Suijk et al32Netherlands31±484 (24)5.5±1.27.3 (0.8)NR
Canagliflozin* (SGLT2i)Davies et al63NR32.0±6.588.8±18.95.3–5.48.0±0.9NR
Luseogliflozin* (SGLT2i)Seino et al64Japan24.8±3.56NR5.09±1.498.07±0.906.15±6.50
Chino et al65JapanNR85±185.1±1.38.1±0.9NR
Tofogliflozin* (SGLT2i)Terauchi et al66Japan25.8±3.579.7±19.85.05±1.258.53±0.7515.02±9.36
Ipragliflozin* (SGLT2i)Tanaka et al67Japan30.5±7.067.3±18.25.7±1.47.0±0.5NR
Tsukagoshi-Yamaguchi et al68Japan29.0±5.7NR5.1±1.48.1±0.74.4±4.9
Nagao et al69JapanNRNR5.5 (4.5–6.2)7.5 (7.1–7.9)NR
Drug classificationReference, yearStudy locationDrug doseDrug durationSerum urate change (mg/dL)P-value
Metformin* (-)Gregorio et al20Italy1000 mg/day progressively increased to 1500 mg/day1 yearFrom 5.88±0.25 to 5.02±0.28p<0.05 vs. baseline
Gliclazide (Sulfonylurea)Kilo et al30USA80-320 mg/day1 yearNo significant changep>0.05 vs. baseline
Suijk et al32Netherlands30 mg/day12 weeksNo significant change during hyperglycemic conditionsp=0.07 vs. baseline
Glimepiride (Suilfonylurea)Kitazawa et al33Japan0.5 mg/day24 weeksNo significant changep=0.773 vs. baseline
Sitagliptin (DDP4i)Matsushima et al34Japan50 mg/day12 weeksFrom 5.08±1.14 to 5.30±1.24p=0.001 vs. baseline
Kutoh et al35Japan25 mg/day for females (n=14), 50 mg/day for males (n=50)3 monthsFrom 4.91±1.28 to 5.42±1.43p<0.00001 vs. baseline
Tojikubo et al36Japan50 mg/dayat least 1 yearFrom 5.10±1.13 to 5.63±1.24p<0.001 vs. baseline
Fuchigami et al37Japan50–100 mg/day24 weeksFrom 5.4±1.4 to 5.6±1.3p=0.004 vs. baseline
Alogliptin (DDP4i)Kutoh et al35Japan12.5 mg/day for females (n=9), 5 mg/day for males (n=46)3 monthsFrom 4.69±1.60 to 5.24±1.61p<0.00001 vs. baseline
Linagliptin* (DDP4i)Tojikubo et al36Japan5 mg/day1 yearFrom 5.63±1.24 to 5.24±1.10p<0.001 vs. baseline
Yamagishi et al38Japan5 mg/day24 weeksFrom 5.5±1.2 to 5.1±1.2p<0.05 vs. baseline
Vildagliptin* (DDP4i)Shimodaira et al39Japan100 mg/day1 yearFrom 6.0 ± 1.6 to 5.3±1.3p<0.05 vs. baseline
Voglibose (alpha-glucosidase inhibitor)Matsushima et al34Japan0.6 mg/day12 weeksNo significant changep=0.073 vs. baseline
Troglitazone* (Thiazolidinedione)Iwatani et al42Japan400 mg/day9.7±7.6 monthsFrom 5.5±1.2 to 5.0±1.2p<0.0001 vs. baseline
Rosiglitazone* (Thiazolidinedione)Seber et al43Turkey4 mg/day12weeksFrom 4.78±1.1 to 4.41±1.1p=0.001 vs. baseline
Macić-Dzanković et al44Sarajevo4 mg/day12 weeksFrom 6.22±1.31 to 6.02±1.27p<0.015 vs. baseline
Pioglitazone* (Thiazolidinedione)Kutoh et al45Japan7.5–30 mg/day12 weeksFrom 6.87±0.73 to 5.90±0.77p<0.00001 vs. baseline
Insulin (-)MacFarlane et al47USANAMean of 2.9 years+1.25p=0.02
Exenatide (GLP-1 RA)Dutour et al51France10–20 µg/day26 weeksNo significant changep=0.79 vs. reference
Muskiet et al52Sweden, Finland, Netherlands20 µg/day52 weeksNo significant changep>0.05 vs. baseline
Liraglutide (GLP-1 RA)Tonneijck et al53Netherlands1.8 mg/day12 weeksNo significant changep=0.8 vs. placebo
Nakaguchi et al54Japan0.9 mg/day24 weeksNo significant changeNR
Kurir et al55Croatia1.2 mg/day3 monthsNo significant changep=0.104 vs. baseline
Liakos et al56Greece1.2 mg/day5 weeksNo significant changep=0.23 vs. placebo
Lixisenatide (GLP-1 RA)Tonneijck et al53Netherlands20 µg/day8 weeksNo significant changep>0.1 vs. baseline
Dulaglutide (GLP-1 RA)Kuchay et al57India1.5 mg/week24 weeksNo significant changep=0.11 vs. control
Hirai et al58Japan0.75 mg/week1 yearNo significant changep>0.05 vs. baseline
Iwasaki et al59Japan0.75 mg/week24 weeksNo significant changep=0.0818 vs. baseline
Empagliflozin* (SGLT2i)You Y et al61NA10 or 25 mg/day5 days to 164 weeksSMD: -1.34p<0.001 vs. placebo
Dapagliflozin* (SGLT2i)Hao Z et al62China10 mg/dayNRFrom 5.86±1.72 to 4.71±1.20p<0.001 vs. baseline
Fuchigami et al37Japan5-10 mg/day24 weeksFrom 5.4±1.3 to 4.9 ± 1.1p<0.001 vs. baseline
Suijk et al32Netherlands10 mg/day12 weeksFrom 5.5±1.1 to 4.6±1.0p<0.001 vs. baseline
Canagliflozin* (SGLT2i)Davies et al63NR100 or 300 mg/day26 weeks−0.7NR
Luseogliflozin* (SGLT2i)Seino et al64Japan2.5 mg/day12 weeks−0.63p<0.05 vs. placebo
Chino et al65Japan2.5 or 5 mg/day12 weeks−0.6p<0.05 vs. baseline
Tofogliflozin* (SGLT2i)Terauchi et al66Japan20 mg/day16 weeks−0.18p=0.0062 vs. placebo
Ipragliflozin* (SGLT2i)Tanaka et al67Japan50 mg/day12 weeksFrom 5.7±1.4 to 5.0±1.3p<0.05 vs. baseline
Tsukagoshi-Yamaguchi et al68Japan50 mg/day24 weeks−11.3 %p=0.012 vs. control
Nagao et al69Japan50 mg/day6 months−0.41p<0.05 vs. baseline

  • ↵* Drugs that decreased serum uric acid.

  • NA: not applicable, NR: not reported, SMD: standardized mean difference, F: female, M: male, N: number, SGLT2i: sodium-glucose cotransporter 2 inhibitors, GLP-RA: glucagon-like peptide-1 receptor agonists, DDP4i: dipeptidyl peptidase 4 inhibitor