Skip to main content

Table 2 Summary of study findings

From: Effectiveness and safety of dipeptidyl peptidase 4 inhibitors in the management of type 2 diabetes in older adults: a systematic review and development of recommendations to reduce inappropriate prescribing

Authors and publication year

Outcomes

DPP-4 inhibitor cases/na (%)

Comparator cases/na (%)

Risk ratiob (95% CI)

Reported Statistical comparison

Result favoursc

Tier 1 outcomes (hypoglycaemia and adverse events), comparisons against placebo

 Barnett et al. 2013 [31]

 QAd = moderate

SAEs

Linagliptin

Placebo

   

14/162 (8.6)

5/79 (6.3)

1.37 (0.51, 3.66)

NR

C

Severe AEs

9/162 (5.6)

3/79 (3.8)

1.46 (0.41, 5.25)

NR

C

Significant AEs

4/162 (2.5)

0/79 (0.0)

4.40 (0.24, 80.8)

NR

C

Hypoglycaemia

37/162 (22.8)

13/79 (16.5)

1.39 (0.78, 2.46)

NR

C

 Barzilai et al. 2011 [30]

 QAd = moderate

 

Sitagliptin

Placebo

   

Clinical AEs

47/102 (46.1)

55/104 (52.9)

0.87 (0.59, 1.29)

Diff in % = −6.8%, (−20.0, 6.7)

D

Clinical SAEs

7/102 (6.9)

14/104 (13.5)

0.51 (0.21, 1.26)

Diff in % = −6.6%, (−15.2, 1.9)

D

Hypoglycaemia

0/102 (0.0)

0/102 (0.0)

1.0 (0.02, 49.9)

NR

Neither

 SAVOR-TIMI 53

 

Saxagliptin

Placebo

   

 Mosenzon et al. 2015 [43]

 Subgroup P > =75

 QAd = high

Bone fracture

57/1169

51/1161

1.11 (0.77, 1.61)

HR = 1.13 (0.77, 1.65)

C

 Schweizer et al. 2013 [53]

 QAd = low

 

Vildagliptin

Placebo

   

AEs

29/50 (58.0)

40/55 (72.7)

0.80 (0.49, 1.29)

NR

D

SAEs

7/50 (14.0)

9/55 (16.4)

0.86 (0.32, 2.30)

NR

D

Hypoglycaemia

0.49 events per patient-year

0.96 events per patient-year

0.53 (0.26, 1.08)

p = 0.970

D

 Shih et al. 2015 [36]

 QAd = low

Hospitalisation for sepsis:

DPP-4 inhibitor use by casese

DPP-4 inhibitor use by controlse

   

Current DPP-4 users only

1148/43015 (2.7)

1152/43015 (2.7)

1.01 (0.93, 1.09)

OR = 0.97 (0.89, 1.07)

D

Used any time in past year

3523/43015 (8.2)

3276/43015 (7.6)

1.09 (1.03,1.14)

OR = 1.01 (0.95, 1.06)

C

 Strain et al. 2013 [52]

 

Vildagliptin

Placebo

   

 QAd = high

AEs

66/139 (47.5)

63/139 (45.3)

1.05 (0.81, 1.35)

NR

C

SAEs

8/139 (5.8)

5/139 (3.6)

1.60 (0.54, 4.77)

NR

C

Hypoglycaemia

3/139 (2.2)

1/139 (0.7)

3.00 (0.32, 28.5)

NR

C

Tier 1 outcomes (hypoglycaemia and adverse events), comparisons against other active treatments

 Banerji et al. 2010 [29]

Normal renal function

Vildagliptin + metformin

TZD + metformin

   

 QAd = low

AEs

54/144 (37.5)

29/84 (34.5)

1.09 (0.76, 1.56)

NR

C

 Subgroup P ≥ 65

SAEs

2/144 (1.4)

1/84 (1.2)

1.17 (0.11, 12.7)

NR

C

 

Mildly impaired renal function

AEs

59/171 (34.5)

32/77 (41.6)

0.83 (0.59, 1.16)

NR

D

SAEs

5/171 (2.9)

4/77 (5.2)

0.56 (0.16, 2.04)

NR

D

 Ferrannini et al. 2009 [54]

 QAd = low

 Subgroup P ≥ 65

Hypoglycaemic events

Vildagliptin

Glimepiride

   

6/351 (1.7)

59/361 (16.4)

0.1 (0.05, 0.24)

NR

D

 Hartley 2015 [37]

 QAd = low

 

Sitagliptin

Glimepiride

   

AEs

118/241 (49.0)

115/236 (48.7)

1.00 (0.84, 1.21)

NR

Neither

SAEs

7/241 (2.9)

6/236 (2.5)

1.14 (0.39, 3.35)

NR

C

Asymptomatic hypoglycemia

16/241 (6.6)

35/236 (14.8)

0.45 (0.25, 0.79)

NR

D

Symptomatic hypoglycemia

2/241 (0.8)

11/236 (4.7)

0.18 (0.04, 0.79)

p = 0.009

D

 Matthews et al. 2010 [55]

 QAd = low

 Subgroup P ≥ 65

 

Vildagliptin

Glimepiride

   

Hypoglycaemia

8/392 (2.1)

69/397 (17.5)

0.12 (0.06, 0.24)

p < 0.001

D

 Penfornis et al. 2012 [49]

 QAd = low

 

DPP-4 inhibitors

COAD

   

Hypoglycaemia

60/931 (6.4)

52/257 (20.1)

0.32 (0.23, 0.45)

p < 0.001

D

Severe hypoglycaemia

1/931 (0.1)

6/257 (2.4)

0.05 (0.01, 0.38)

p = 0.001

D

 Rosenstock et al. 2013 [59]

 QAd = low

 

Alogliptin

Glipizide

   

Hypoglycaemia

12/222 (5.4)

57/219 (26.0)

0.21 (0.11, 0.39)

NR

D

AEs

163/222 (73.4)

151/219 (68.9)

1.06 (0.85, 1.33)

NR

C

SAEs

16/222 (7.2)

13/219 (5.9)

1.21 (0.58, 2.52)

NR

C

 Schernthaner et al. 2015 [59]

 QAd = low

 

Saxagliptin + metformin

Glimepiride + metformin

   

Hypoglycaemia

21/359 (5.8)

125/359 (34.8)

0.17 (0.11, 0.26)

NR

D

Severe hypoglycaemia

4/359 (1.1)

55/359 (15.3)

0.07 (0.03, 0.20)

OR = 0.06 (0.02, 0.17)

D

AEs (excluding hypoglycaemia)

213/359 (59.3)

213/359 (59.3)

1.00 (0.89, 1.13)

NR

Neither

SAEs

41/359 (11.4)

32/359 (8.9)

1.28 (0.83, 1.99)

NR

C

Deaths

1/359 (0.3)

1/359 (0.3)

1.00 (0.06, 15.93)

NR

Neither

 Schweizer et al. 2009 [40]

 QAd = low

 

Vildagliptin

Metformin

   

AEs

74/167 (44.3)

83/165 (50.3)

0.88 (0.70, 1.11)

NR

D

SAEs

5/167 (3.0)

6/165 (3.6)

0.82 (0.26, 2.65)

NR

D

Gastrointestinal AEs

25/167 (15.0)

41/165 (24.8)

0.60 (0.38, 0.94)

NR

D

Hypoglycaemia

0/167 (0.0)

2/165 (1.2)

0.20 (0.01, 4.09)

NR

D

 Sicras-Mainar and Navarro-Artieda 2014 [50]

 QAd = very low

 

Vildagliptin + metformin

Sulfonylureas + metformin

   

Hypoglycaemia

47/270 (17.4)

307/717 (42.8)

0.41 (0.31, 0.53)

p < 0.001

D

 Viljoen et al. 2013 [46]

 QAd = very low

 

DPP-4 inhibitors

Never treated with DPP-4

   

Hypoglycaemia

4/129 (3.1)

24/302 (7.9)

0.39 (0.14, 1.10)

p = 0.062

D

 Driessen et al. 2014 [45]

 QAd = low

Fractures

DPP-4 inhibitor

Other non-insulin anti-diabetic drugs

   

70–79 years

NR

NR

 

HR = 1.16 (0.95, 1.42)

C

80 + years

NR

NR

 

HR = 1.0 (0.74,1.34)

Neither

Tier 1 outcomes (hypoglycaemia and adverse events), DPP-4 inhibitors as an additional treatment

 Chien et al. 2011 [32]

 QAd = low

 

Sitagliptin + OAD combinations

OAD combinations

   

AEs

5/49 (10.2)

3/49 (6.1)

1.67 (0.40, 6.97)

NR

C

Hypoglycaemia

1/49 (2.0)

0/49 (0.0)

3.0 (0.13, 71.9)

NR

C

 Kadowaki et al. 2014 [38]

 Subgroup P ≥ 65

 QAd = low

 

Teneligliptin + glimepiride

Placebo + glimepiride

   

AEs (including hypoglycaemia)

0/27 (0.0)

1/34 (2.9)

0.42 (0.02, 9.87)

NR

D

ADRs (including hypoglycaemia)

0/27 (0.0)

1/34 (2.9)

0.42 (0.02, 9.87)

NR

D

Tier 2 outcomes (cardiovascular outcomes), comparisons against placebo

 Johansen et al. 2012 [58]

 QAd = low

 Subgroup P ≥ 65

 

Linagliptin

Comparatorsf

   

Fatal or non-fatal MI or stroke, or hospitalisation for unstable angina pectoris

5/929 (0.5)

14/549 (2.6)

0.21 (0.08, 0.58)

HR = 0.28, (0.1–0.79)

D

 TECOS

 Green et al. 2015 [13]

 QAd = low

 Subgroup P ≥ 65

 

Sitagliptin

Placebo

   

Composite CV outcome (first confirmed event of CV death, non-fatal MI, nonfatal stroke, or hospitalization for unstable angina)

NR

NR

 

HR = 1.01 (0.90, 1.15)

C

 SAVOR-TIMI 53

 Scirica et al. 2013 [12]

 Scirica et al. 2014 [41]

 Subgroup P ≥ 75

 Leiter et al. 2015 [42]

 Subgroup P ≥ 65

 QAd = high

Subgroup P ≥ 75

Saxagliptin

Placebo

   

CV death, nonfatal MI, or nonfatal ischemic stroke

117/1169 (10.0)

129/1161 (11.3)

0.90 (0.71, 1.14)

HR = 0.96 (0.75, 1.22)

D

Hospitalisation for HF Subgroup P ≥ 65

79/1169 (6.8)

57/1161 (4.9)

1.38 (0.99, 1.92)

HR = 1.47 (1.05, 2.08)

C

CV death, nonfatal MI, or nonfatal ischemic stroke

334/4290 (7.8)

367/4271(8.6)

0.91 (0.79, 1.04)

HR = 0.92 (0.79, 1.06)

D

CV death, MI, stroke, hospitalization for unstable angina, HF, or coronary revascularization

570/4290 (13.3)

593/4271(13.9)

0.96 (0.86, 1.06)

HR = 0.96 (0.85, 1.07)

D

MI

141/4290 (3.3)

170/4271(4.0)

0.83 (0.66, 1.03)

HR = 0.86 (0.69, 1.07)

D

CV mortality

158/4290 (3.7)

166/4271(3.9)

0.95 (0.77, 1.17)

HR = 0.92 (0.74, 1.13)

D

Non-CV mortality

98/4290 (2.3)

76/4271(1.8)

1.28 (0.95, 1.73)

HR = 1.22 (0.92, 1.63)

C

All-cause mortality

253/4290 (5.9)

239/4271(5.6)

1.05 (0.89, 1.25)

HR = 1.01 (0.86, 1.20)

C

Nonfatal ischemic stroke

77/4290 (1.8)

68/4271(1.6)

1.13 (0.82, 1.56)

HR = 1.17 (0.85, 1.61)

C

Hospitalisation for/due to:

CR

210/4290 (4.9)

234/4271(5.5)

0.89 (0.75, 1.07)

HR = 0.87 (0.73, 1.05)

D

HF

180/4290 (4.2)

149/4271(3.5)

1.20 (0.97, 1.49)

HR = 1.25 (1.01, 1.56)

C

Hypoglycaemia

34/4290 (0.8)

25/4271(0.6)

1.35 (0.81, 2.27)

HR = 1.29 (0.78, 2.14)

C

Unstable angina

38/4290 (0.9)

38/4271(0.9)

1.00 (0.64, 1.56)

HR = 0.89 (0.56, 1.39)

D

 White et al. 2013 [44]

 QAd = low

 

Alogliptin

Placebo

   

Death from CV causes, or nonfatal MI or stroke

141/934 (15.1)

149/973 (15.3)

0.99 (0.8, 1.22)

HR = 0.98 (0.78, 1.24)

D

Tier 2 outcomes (cardiovascular outcomes), comparisons against other active treatments

 Chang et al. 2015 [33]

 Subgroup P ≥ 65

 QAd = low

 

DPP-4 inhibitors plus metformin

Sulfonylureas plus metformin

   

Any CV event

NR

NR

 

HR = 0.86 (0.72, 1.02)

D

MI

NR

NR

 

HR = 0.86 (0.44, 1.70)

D

HF

NR

NR

 

HR = 1.01 (0.72, 1.43)

C

Ischaemic stroke

NR

NR

 

HR = 0.83 (0.68, 1.02)

D

 Chen et al. 2015 [34]

 Subgroup P ≥ 75

 QAd = low

 

Sitagliptin

Non-sitagliptin

   

Composite of ischemic stroke, MI, or CV death

59/486 (12.1)

104/949 (11.0)

1.11 (0.82, 1.50)

p = 0.463

C

Ischemic stroke

42/486 (8.6)

77/949 (8.1)

1.07 (0.74, 1.53)

p = 0.705

C

 Giorda et al. 2015 [48]

 QAd = low

 

DPP-4 inhibitor use by casese

DPP-4 inhibitor use by controlse

   

Any admission for HF

256/14613 (1.8)

2881/146130 (2.0)

0.89 (0.78, 1.01)

OR = 1.00 (0.94, 1.07)

Neither

Incident HF

135/7212 (1.9)

1285/72120 (1.8)

1.05 (0.88, 1.25)

OR = 1.01 (0.92, 1.11)

C

Re-admission for HF

37/1727 (2.1)

338/17222 (2.0)

1.09 (0.78, 1.53)

OR = 1.02 (0.84, 1.22)

C

All-cause mortality

306/38248 (0.8)

6717/382313 (1.8)

0.46 (0.41, 0.51)

OR = 0.94 (0.90, 0.98)

D

 Ou et al. 2015 [35]

 Subgroup P 61–80

 Subgroup P ≥ 81

 QAd = low

 

DPP-4 inhibitors + metformin

Sulfonylureas + metformin

   

All-cause mortality

61–80

NR

NR

 

HR = 0.57 (0.46, 0.71)

D

P ≥ 81

NR

NR

 

HR = 0.61 (0.43, 0.87)

D

MI

61–80

NR

NR

 

HR = 0.47 (0.26, 0.83)

D

P ≥ 81

NR

NR

 

HR = 0.70 (0.25, 2.00)

D

Ischemic stroke

61–80

NR

NR

 

HR = 0.49 (0.24, 1.00)

D

P ≥ 81

NR

NR

 

HR = 0.63 (0.50, 0.80)

D

Hospitalisation for HF

61–80

NR

NR

 

HR = 0.78 (0.52, 1.16)

D

P ≥ 81

NR

NR

 

HR = 0.33 (0.13, 0.87)

D

 Rosenstock et al. 2013 [59]

 QAd = low

 

Alogliptin

Glipizide

   

Major adverse cardiac events

1/222 (0.5)

2/219 (0.9)

0.49 (0.04, 5.44)

NR

D

 Schweizer et al. 2009 [40]

 QAd = low

 

Vildagliptin

Metformin

   

CV and cerebrovascular events

2/167 (1.2)

2/165 (1.2)

1.0 (0.14, 6.93)

NR

Neither

 Sicras-Mainar and Navarro-Artieda 2014 [50]

 QAd = very low

 

Vildagliptin + metformin

Sulfonylureas + metformin

   

CV events

12/270 (4.4)

62/717 (8.6)

0.51 (0.28, 0.94)

p = 0.025

D

Ischemic heart disease

2/270 (0.7)

15/717 (2.1)

0.35 (0.08, 1.54)

p = 0.043

D

Cerebrovascular accident

6/270 (2.2)

31/717 (4.3)

0.51 (0.22, 1.22)

p = 0.042

D

Renal failure

4/270 (1.5)

16/717 (2.2)

0.66 (0.22, 1.97)

p = 0.138

D

 Tziomalos et al. 2015 [51]

 QAd = very low

 

DPP-4 inhibitors

Other antidiabetic drugs

   

In-hospital mortality in people admitted with acute ischaemic stroke

0/27 (0.0)

11/73 (15.1)

0.12 (0.01, 1.91)

p < 0.05

D

Modified Rankin Scale of disability [mean (SD)]

2.1 (1.9)

3.2 (2.1)

 

p < 0.05

D

 Yu et al. 2015 [47]

 QAd = low

 

DPP-4 inhibitor use by casese

DPP-4 inhibitor use by controlse

   

Hospitalisation for HF

54/1118 (4.8)

808/17626 (4.6)

1.05 (0.81, 1.38)

OR = 0.88 (0.63, 1.22)

D

  1. AEs Adverse events, ADRs Adverse drug reactions, C Comparator, CI Confidence interval, COAD Conventional oral antidiabetic drugs, CV Cardiovascular, D DPP-4 inhibitor, Diff Difference, HF Heart failure, HR Hazard ratio, MI Myocardial Infarction, CR Coronary revascularization, NR Not Reported, OAD Oral anti-diabetic agents, P Participants, SAEs Serious adverse events, anumber of patients with the outcome/total patients, unless stated otherwise; bZero cell adjustment applied where relevant; cBased on reported comparison or if not reported, the computed risk ratio; d QA: quality appraisal based on study limitations suggested by Guyatt et al. (2008) [26]; e Case-control study: cases are patients with the outcome, controls are matched patients without, numerator is count of patients using DPP-4 inhibitors; fData pooled over 8 trials, 6 comparing against placebo only
Back to article page

BMC Geriatrics

ISSN: 1471-2318

Contact us