Table 6. Review of studies on diabetes mellitus 2 in the elderly.
| Studies | Quality assessment | Summary of findings | Quality | |||||||||
| Ref | N | Study desing | Limitations | Inconsistency | Indirectness | Imprecision | Publication Bias |
Relative effect estimates | Absolute effect estimates | |||
| CS: cohort study; DM2: type 2 diabetes; DPP-4 (dipeptidylpeptidase-4) inhibitor; HR: Hazard ratio; I: Important; MET: metformin; NA: Not Applicable; OBS: observational study; OR: odds ratio; PBO: placebo; PIO: pioglitazone; Quality: quality assessed according to GRADE methodology; RCT: random clinical trial; Ref: bibliography reference annex 1; SR: systematic review; SPPB: short physical performance battery; SULF: sulfonylurea; TZD: Thiazolidinediones; U: Undetected; UV: unavailable; VI: very Important; vs: versus. | ||||||||||||
| What is the therapeutic target in the elderly with DM2? | ||||||||||||
| 60 | 3 475 1 732 (with treatment) |
RCT Post hoc analysis |
I | U | U | I | U | Non fatal Acute myocardial infarction + non fatal stroke+ cardiovascular mortality: HR 0.84 (0.69-1.03) |
2.76% (intensive treatment) vs 3.10% (standard treatment) |
Low | ||
| 61 | 6 611 | RCT Subgroup analysis |
I | U | U | I | U | Macro and microvascular damage: RR 0.92 (0.83-1.03) |
19.5% (intensive treatment) vs 21% (Standard treatment) |
Low | ||
| 62 | 1 173 585 (with treatment) |
RCT | I | U | U | I | U | No significant difference in fatal events Significative difference coronary revascularization |
No diference significative in mortality events Significative difference coronary revascularization |
Low | ||
| What is the therapeutic target in frail elderly with DM2? | ||||||||||||
| 63 | 25 966 (with treatment) | CS | U | U | NA | U | U | Adjusted mortality: RR-(0.80 (0.70-0.91) (Subgroup HbA1 7-7.4 vs HbA1 8-8.4%) No differences between reference group and HbA1 <6->8.5% |
80.9 por 1000 Patients/year (subgroupHbA1 7-7.4%) |
Low | ||
| 64 | 993 497 (with treatment) | RCT POST HOC ANALYSIS |
I | U | U | I | U | Higher risk of stroke in subgroup HbA1 >8.8%- 6-7.2% |
UV | Low | ||
| 65 | 232 (with treatment DM) 1 835 (with treatment Not for DM) |
CS | I | U | NA | I | U | RR 1.40 (1.12-1.76) p=0.002 Dementia (Hiperglycemia 190 mg/dl) |
UV | Low | ||
| 66 | 200 (with treatment DM) 1 648 (with treatment Not for DM) |
CS | I | U | NA | I | U | Risk of frailty (p=0.001) (Glucose < 160 - > 180 mg/dl) |
UV | Low | ||
| 67 | 446 (with treatment) | CS | I | U | NA | I | U | Risk if falls with insuline OR 4.36 (1.32-14.46) (HbA1 ≤6 vs >8%) |
UV | Low | ||
| 68 | 132 (with treatment) | CS | I | U | NA | I | U | More frailty: strict HbA1 controls |
UV | Low | ||
| 69 | 111 (with treatment) | CS | I | U | NA | I | U | Risk of falls (p=0.01) (HbA1 < 7%) | UV | Low | ||
| What is the therapeutic target in elderly people with established functional impairment with dm2? | ||||||||||||
| 70 | 367 (with treatment) | CS | I | U | NA | I | U | Lower functional decline and mortality RR 0.88 (0.79-0.99) (HbA1 8-8.9% vs HbA1 7-7.9%) | 52% vs 58% | Low | ||
| 71 | 119 (with treatment) | CS | I | U | NA | I | U | Better lower extremity functionality (SPPB test): Lower variability in glucosa control (HbA1 <7%) | UV | Low | ||
| What is the therapeutic target in the elderly with several cvrf for each of them? | ||||||||||||
| 72 | 388 (with treatment) | CS | I | U | NA | I | U | No higher mortality risk with HbA1 7%. blood pressure 145/80 mmHg and total cholesterol < 240 mg/dl Higher mortality depending on terminal kidney disease and macroangiopathy (previous stroke, obesity and hiher levels of LDL) |
19.6% Mortality (6years) | Low | ||
| Efficacy of pharmacological treatment in the elderly: metformin | ||||||||||||
| 73 | 1 273 (with treatmentMET) | CS | I | U | NA | I | U | Reduction of annual mortality risk from any cause HR 0.87 (0.78-0.97) (MET vs other treatments) |
24.7% vs 36% | Low | ||
| 74 | 1 273 (with treatment MET) | CS | I | U | NA | I | U | Annual mortality HR 0.92 (0.81-1.06) (MET VS treatment other treatments) | UV | Low | ||
| 75 | 367 (with treatment) | CS | I | U | NA | VI | U | Higher mortality risk: (MET + strict glycemia control < 6.5%) HR 2.63; 1.39-4.97 |
UV | Very low | ||
| 76 | 8 393 (with treatmenttMET) | CS | U | U | NA | U | U | Lower mortality risk MET |
UV | Low | ||
| Efficacy of pharmacological treatment in the elderly: pioglitazone | ||||||||||||
| 74 | 819 (with treatment TZD) | CS | I | U | NA | I | U | Reduction of annual mortality from any cause HR 0.87 (0.80-0.94) Higher risk with heart failure HR 1.06 (1-1.09) |
30.1% vs 36% | Low | ||
| 73 | 2 276 (with treatment TZD) | CS | I | U | NA | I | U | Annual mortality HR 0.92 (0.80-1.05) Higher risk of readmission (1.09;1-1.20) Higher risk of readmission for heart failureHR 1.17 (1.05-1.3). |
UV | Low | ||
| 77 | 69 (with treatment TZD) 30 (with treatment PIO) |
CS | I | U | NA | I | U | Increased bone loss TZD (women): HR -0.61 ( -1.02-0.21) |
UV | Low | ||
| Efficacy of pharmacological treatment in the elderly: sulfonylureas | ||||||||||||
| 73 | 12 069 (with treatment) | CS | I | U | NA | I | U | Reduction of mortality TZD/MET not with Sulfonylureas (0.99;0.91-1.08) Higher risk of stroke ( TZD) Higher risk of readmission for heart failure (1.06;1-1.09) (TZD) |
UV |
Low | ||
| 75 | 130 N TTO SLF | CS | I | U | NA | VI | U | Higher risk of mortality Sulfonylureas (strict control of HbA1 < 7%) HR 2.49 (1.14-5.44) | UV | Very low | ||
| 78 | 5 543 (with treatment SLF) | CS | I | NA | NA | I | U | Composite outcome (mortality +atrial fibrilation +stroke+heart failure+ Acute myocardial infarction): gliburide/glipizide/repaglinide HR 0.91 (0.78-1.05) |
28.1% 30.2% 23.4% |
Low | ||
| 79 | 13 963 (with treatment SLF) | CS | I | U | NA | U | U | High risk of severe hypoglycemia: gliburide HR 16.6 (13.2-19.9) Loser risk: tolbutamide and glipicide Same high risk gliburide =clorpropamide |
gliburide (16.6/1.000 patients/year; 13.2-19.9) lower rates (3.5; 1.2-5.9) (tolbutamide and glipicide) |
Low | ||
| 80 | 139 N TTO | ECA | I | I | U | I | U | UV | Glycemia control: 80.3% glubiride vs 64.4% glipizide |
Low | ||
| Efficacy of pharmacological treatment in the elderly: metiglinide | ||||||||||||
| 78 | 740 (with treatment repaglinide) | CS | I | NA | NA | I | U | Composite outcome (mortality +atrial fibrilation +stroke+heart afilure+ Acute myocardial infarction): Repaglinide HR 0.80 (0.63-1.03) no significative differences vs glipizide/gliburide |
28.1% 30.2% 23.4% |
Low | ||
| 81 | 54 30 (with treatment) |
RCT | I | U | U | I | U | UV | Reduction HbA1 (12 weeks) Treatment (7.6±0.1%) vs basal control (6.9±0.1%) Difference -0.7±0.1% (P<0.001) vs PBO (-0.5. p=0.004) |
Low | ||
| 81 | 66 33 (with treatment) |
RCT SUBANALYSIS |
I | U | U | I | U | UV | Reduction HbA1 (104 SE): nateglinide/MET (7.8±0.2%) vs basal level (6.6±0.1%) differences -1.2±0.2%. (P<0.001) Reduction HbA1 (104 weeks): gliburide/MET (7.7±0.1) vs BASAL (6.5±0.2%) differences1.2±0.1% (p<0.001) no significative difference (p=0.310) |
Low | ||
| Efficacy of pharmacological treatment in the elderly: ddp-4 inhibitors | ||||||||||||
| 82 | 241 | RCT | U | U | U | I | U | More reduction HbA1: linagliptine −0.64% (95% CI −0.81-−0.48) (p<0.0001) |
linagliptine –0.61% (0.06) vs PBO 0.04% (0.07) |
Moderate | ||
| 83 | 278 | RCT | ND | U | U | I | U | Greater % achievement of objective HbA1: Vidalgiptine OR 3.16 (1.81-5.52) |
Vidagliptine 52.6% vs 27% PBO | Moderate | ||
| 84 | 388 | RCT | I | U | U | U | U | Better control HbA1: sitagliptine and glimeridae DIF 0.19% (0.03-0.34%) | -0.32% (sitagliptine) vs -0.51% (glimeride) |
Moderate | ||
| 85 | 441 | RCT | I | U | U | U | U | Reduction HbA1: alogliptine vs tto glipicide (-0.05% -0.13%) | -0.14% (alogliptine) vs 0.09% (glipicide) |
Moderate | ||
| 86 | 720 | RCT | U | U | U | U | U | HbA1 < 7% (52 weeks): saxagliptine vs tto glimepiridE OR 0.99 (0.73-1.34) | 37.9% vs 38.2% | High | ||
| 87 | 201 | RCT | U | U | U | U | U | Higher reduction of HbA1 and postpandrial glucose (2hours): sitagliptine | sitagliptine: difference 0.7% and 61 mg/dl | High | ||
| 88 | 335 | RCT | I | U | U | U | U | Reduction HbA1: No differences with vildagliptine | (-0.64 ± 0.07% and -0.75 ± 0.07%) | Moderate | ||
| 89 | 58 485 | CS | U | U | NA | U | U | Lower mortality: DPP4 Inh Vs no treatment (HR=0.54;0.52-0.56) Treatment for myocardial infarction, cerebrovascular accident or cardiovascular death vs no treatment (HR=0.79; 0.75-0.83) |
Mortality incidence (1000/year) (DPP4 I vs no treatment): 36.01 y 66.91 / myocardial infarction, cerebrovascular accident or cardiovascular death (26.37 y 33.41) acute myocardial infaction (6.76 8.58) stroke (20.34 y 25.85) |
Moderate | ||
| 90 | 35 206 (with treatment SULF) 9 517 (with treatmentTZD) |
CS | I | U | NA | U | U | Reduction of non- mortal infarct < DPP4 I vs SULF excepting those with MTF as base treatment: (-0.92 (-1.60, -0.24). Composite outcome VS Tiazolidinedione: -0.38 (-0.71, -0.05) Global mortality: -0.44 (-0.83, -0.06) |
Non fatal infarction (100 patients/year): 0.4 (0.2 a 0.6) (DPP4 I) 1.0 (0.8 a 1.2) (SULF) Combinated outcome: 3.9 (3.5 a 4.3) (DPP4 I) 4.5 (3.8 a 5.2) (TZD) Global mortality: 2.9 (2.6 a 3.3) (DPP4 I); 3.5 (2.9 a 4.1) (TZD) |
Low | ||
| Efficacy of pharmacological treatment in the elderly: GLP-1 receptor agonist | ||||||||||||
| 91 | 350 174 (with treatment) |
RCT | I | U | U | U | U | Higher reduction HbA1: lixixenatide |
- 0.57% (lixixenatide) vs +0.06% (PBO) (p<0.0001) | Moderate | ||
| Efficacy of pharmacological treatment in the elderly: alpha glucosidase inhibitors | ||||||||||||
| 92 | 192 93 (with treatment) |
RCT | I | U | U | I | U | UV | Reduction HbA1 (1 A): TTO acarbose -0.6±1 vs PBO | Low | ||
| 93 | 45 22 (with treatment) |
RCT | MI | U | U | I | U | UV | Blood glucose reduction fasting: 0.2 ± 0.3 (treatment) vs. -0.5 ± 0.2 mmol/l (PBO) (P < 0.05) |
Low | ||
| Efficacy of pharmacological treatment in the elderly: insuline | ||||||||||||
| 73 | 12 069 (with treatment) | CS | I | U | NA | I | U | Anual mortality for any cause: HR 0.96 (0.88-1.05) |
UV | Low | ||
| 94 | 130 (with treatment) | RCT | I | U | NA | I | U | UV | Reduction HbA1 -1.9% vs 1.4% (insuline subgroup + other hypoglycemia Treatment vs regular mixte insuline+ Human protamine) higher % HbA1 ≤7% + without nocturn hypoglycemia 55.2% vs 30.2% (p=0.006). |
Moderate | ||
| What are the effects associated with overtreatment in the elderly? | ||||||||||||
| 95 | 65 (with treatment) | CS | I | U | NA | I | U | UV | Reduction HbA1 -0.52% (0.5%) (HBA1 8-9%) p<0.001) vs Increase HbA1 0.37% (0.7%) (HBA1<7%) p=0.03) |
Low | ||
| 96 | 133 (with treatment) | CS | I | U | NA | I | U | UV | 67% (HbA1 <7%) 10.5% (hypoglycemia episodes in previous year) |
Low | ||
| 97 | 15 643 (with treatment) | CS | U | U | NA | U | U | UV | 52% strict control HbA1 (<7%) Moreover in comorbid patients older and recent weight loss |
Low | ||
| 98 | 42 669 (with treatment) | CS | I | U | NA | U | U | UV | 26% strict control: Higher risk of hypoglycemia in pharmacological group |
Low | ||
| 99 | 8 (with treatment) | OBS | MI | U | NA | VI | U | UV | HbA1: with treatment (HbA1 6.2%±0.8) vs without treatment (6.5%±0.7) | Very low | ||
| 100 | 32 (with treatment) | OBS | MI | U | NA | VI | U | UV | HbA1: with treatment (HbA1 5.2%±0.4) vs without treatment (5.8%±0.9) | Very low | ||
| 101 | 4 368 (with treatment) | CS | I | U | NA | U | U | Withdrawal of treatment: 1.28 (1.22-1.33) | Withdrawal of treatment: 71.5% intervention group VS 56% no intervention group |
Low | ||
| 102 | 2 830 (with treatment) | CS | ND | U | NA | U | U | UV | Withdrawal of treatment: 9.6% (37% hypoglycemia antecedents) | Low | ||
| How does chronic kidney disease modify therapeutic options in the elderly with diabetes? | ||||||||||||
| 103 | 4 053 1 147 (N ≥ 65years) |
SR RCT | U | U | U | U | U | Reduction HbA1: (<≥ 65years) + (glomerular filtration >60 ml/min) |
Lower reduction (≥ 65Ayears and glomerular filtration 45-60 ml/min) | Low | ||
| How does chronic heart failure modify therapeutic options in the elderly with diabetes? | ||||||||||||
| 104 | 1 833 773 (with treatment SULF) 208 (with treatment MET) |
CS | U | U | NA | I | U | UV | Mortality and hospitalization: 52% y 85% SULF vs 33% 77% MET vs 31% y 80% combined |
Low | ||
| 105 | 1 633 (with treatment) | OBS | U | U | NA | I | U | Mortality: MET vs no treatment OR 0.65 (0.48-0.87) MET/other hypoglycemic treatments Vs no hypoglycemic treatments OR 0.72 (0.59-0.90) No reduction of mortality with insuline or hypoglycemic treatments |
UV | Low | ||
| 106 | 217 (with treatment SULF) 68 (with treatment MET) |
CS | U | U | NA | I | U | Mortality MET + combined treatment vs Sulfonylureas 0.59 (0.36-0.96) At long term (0.67; 0.51-0.88) |
UV | Low | ||
| What are the therapeutic options in the elderly with diabetes and frailty? | ||||||||||||
| 107 | 451 (with treatment) | RCT | U | U | U | U | U | Improvement SPPB: 0.85 (0.44-1.26) | Improvement SPPB: 0.83 (0.58 -1.11) | High | ||