Impact statements
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More studies that assess potentially inappropriate prescribing in low- and middle-income countries, nursing homes and community dwelling settings are needed.
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Explicit tools specifically designed to identify potentially inappropriate prescribing for adults living with diabetes are lacking.
Introduction
Aim
Method
Study selection
Search strategy
Extraction of results
Data synthesis
Results
Study selection
Study characteristics
Variable | Category | Number (%) |
---|---|---|
Year of publication
| Before 2000 | 6 (3.2%) |
2000–2009 | 40 (21.1%) | |
2010 and after | 144 (75.8%) | |
Article type
| Original article | 173 (91.1%) |
Case report | 8 (4.2%) | |
Review | 2 (1.1%) | |
Thesis | 7 (3.7%) | |
Language of publication
| English | 174 (91.6%) |
Non-English | 16 (8.4%) | |
Study area
| High-income countries | 121 (63.7%) |
Low- and middle-income countries | 68 (35.8%) | |
Study methodology
| Cross-sectional | 142 (74.7%) |
Cohort | 28 (14.7%) | |
Interventional | 16 (8.4%) | |
Not reported | 4 (2.1%) | |
Study setting
| Outpatient | 100 (52.6%) |
Inpatient | 70 (36.8%) | |
Community dwelling | 17 (8.9%) | |
Nursing home | 8 (4.2%) | |
Not reported | 10 (5.3%) |
Criteria for assessment of PIP
Types of PIP and Standard References/Criteria | Number of Studies (%)a | |
---|---|---|
Types of PIP
| Contraindication (CI) | 91 (47.9%) |
Prescribing omission (PO) | 78 (41.1%) | |
Dosing problem (DP) | 65 (34.2%) | |
Drug-drug interaction (DDI) | 56 (29.5%) | |
Inappropriate drug selection (IDS) | 41 (21.6%) | |
Unnecessary drug therapy (UDT) | 37 (19.5%) | |
Standard References/
Criteria
| Clinical practice guidelines | 66 (34.7%) |
ADA guideline | 19 (10.0%) | |
Malaysian clinical practice guideline | 6 (3.2%) | |
NICE guideline | 5 (2.6%) | |
Canadian clinical practice guideline | 3 (1.6%) | |
Others | 44 (23.2%) | |
Explicitly listed criteria (tools) | 51 (26.8%) | |
STOPP Criteria | 22 (11.6%) | |
START Criteria | 18 (9.5%) | |
Beers criteria | 22 (11.6%) | |
Medication Assessment Tool (MAT) | 2 (1.1%) | |
Othersb | 8 (4.2%) | |
Medication/disease information software and websites | 31 (16.3%) | |
Micromedex | 18 (9.5%) | |
Medscape | 6 (3.2%) | |
Drugs.com | 3 (1.6%) | |
Lexicomp | 3 (1.6%) | |
Othersc | 6 (3.2%) | |
Summary of medicinal product characteristics (SMPC) | 23 (12.1%) | |
Books | 14 (7.4%) | |
Not reported | 34 (17.9%) |
Types of PIP studied
Specific PIP events and medications involved
Type of PIP | Specific PIP events (examples) |
---|---|
Contra
indication
|
Prescribing –
• metformin for a patient with elevated SCr concentration (e.g. SCr > 0.132 mmol/L, SCr ≥ 1.4 mg/dL for women and ≥ 1.5 mg/dL for men, eGFR < 30 mL/min/1.73 m2, AKI/CKD, GFR < 45 mL/min, GFR < 60 mL/min/1.73 m2), lactic acidosis, pH < 7.35, DKA, use of contrast dye, acute MI, cardiac failure, IHD, CAD, hepatic impairment, dehydration, alcoholism (acute or chronic), respiratory failure, gangrene, pancreatitis, circulatory collapse, stress, metabolic diseases, undergoing surgery, age > 80 years, peripheral vascular disease or proteinuria • sulphonylureas for an older adult (e.g. aged ≥ 75 years), history of HF, unstable angina, CHD, stroke, MI, chronic renal insufficiency (moderate to severe), CKD stage ≥ 3b, history of severe hypoglycaemia, obesity, cognitive impairment, and risky occupation (bus/taxi/train driver, working at height), history of DKA, metabolic acidosis, treatment with bosentan or severe hepatic impairment • glyburide for a patient with CrCl < 50 mL/min, eGFR < 60 mL/min/1.73 m2, or frequent occurrence of hypoglycaemic episodes • a long-acting sulfonylurea (e.g. glyburide/glibenclamide, glimepiride, chlorpropamide) for an older T2DM patient (age > 65, age > 45) • insulin aspart, lispro or regular insulin for an older diabetic patient (age ≥ 65) • β-blockers in a diabetic patient with frequent episodes of hypoglycaemia (≥ 1 episode per month), chronic airways disease, taking oral hypoglycaemics or insulin, or older and frail DM patient • metformin for a patient aged 85 years old or above • TZDs in a patient with moderate to severe HF, in AHA class III or IV CHF, liver failure or without investigation of its function, < 18 years old, history of T1DM, concomitantly with metformin in the presence of renal inefficiency, or pregnancy • α-1 blockers, amiodarone, short-acting or immediate release nifedipine, glimepiride, amitriptyline or drugs categorized as high risk in Beers criteria for an older patient • ACEIs for a patient with ESRD • spironolactone for a patient with eGFR < 30 mL/min • aspirin for a patient with CrCl < 10 mL/min • pregabalin fora patient with dizziness, angioedema, decreased platelet count, or non-epileptic seizures • duloxetine for a patient with uncontrolled hypertension, severe renal disease, slow gastric emptying, hyponatremia, urinary hesitation and/or retention, hepatic insufficiency, bipolar disorder, alcohol use, moderate-high severity skin reaction, narrow-angle glaucoma, or non-epileptic seizures • insulin for a patient with BG < 3.9 mmol/l or hypoglycaemia • DPP-4 inhibitors for a patient with hypoglycaemia and concomitant use of insulin or sulphonylurea and pancreatitis • biguanides (e.g. phenformin, metformin) for a high-risk patient for lactic acidosis (e.g. renal insufficiency) • GLP-1 agonist in CKD stage ≥ 4 • gliflozins (SGLT2 inhibitors) for a patient with GFR < 45 mL/min • gliclazide for patient with renal impairment • pioglitazone for a patient having osteoporosis |
Prescribing omission
|
Not prescribing –
• antiplatelets (e.g. aspirin, clopidogrel) for an eligible patient (adult with major cardiovascular risk factors, history of CVD, HTN, hypercholesterolemia, smoking history, TIA/stroke, age ≥ 30 years, or ≥ 40 years, history of atherosclerotic cardiovascular disease in a patient with sinus rhythm, CHD or high risk for CHD, macrovascular disease, IHD, PVD, nephropathy, or microalbuminuria) • lipid lowering therapy (e.g. statin) for an eligible patient (adult with high cardiovascular risk, age > 40 years, history of CVD where the patient’s functional status remains independent for daily activities and life expectancy is more than 5 years, CKD, diabetes duration longer than ten years, HTN, cigarette smoker, family history of early CAD, or albuminuria) • ACEIs/ARBs for an adult with uncontrolled blood pressure, diabetic nephropathy, albuminuria (> 30 mg/24 h), chronic HF, MI, HTN with a history of HF, left ventricular hypertrophy, IHD, CKD, or cardiovascular accident • metformin for an overweight T2DM patient, a T2DM patient ± metabolic syndrome • antihypertensive therapy for hypertensive patient • β-blockers for a T2DM patient with MI, CHF, or HTN + IHD • dual antihypertensive agent for a stage II hypertensive patient • insulin after hypoglycaemia • tricyclic antidepressant for a patient with diabetic neuropathy • fibrates for an adult with TG > 4.5 mmol/L |
Dosing problem
|
Prescribing –
• incorrect insulin dose (high dose, low dose, dose not adjusted when BG persistently > 14 mmol or < 4 mmol, incorrect sliding scale, or sliding scale for an older patient) • incorrect metformin dose (high dose, incorrect dose and interval, thrice daily dosing for SR preparation, dose not adjusted for renal failure, above 1500 mg/d in CKD stage 3a, above 1000 mg in CKD stage 3b, or > 2.5 g/day for older an adult) • unadjusted dose for renal function (unadjusted dose of oral antidiabetic drugs, hypoglycaemic sulfamide, DPP-4 inhibitors, sitagliptin, simvastatin, furosemide, or statin) • high dose digoxin for an older adult (≥ 0.125 mg/d except for treating atrial arrhythmias) • glibenclamide with incorrect dose and interval • unadjusted dose of oral antidiabetic drugs when blood glucose is > 14 mmol or < 4 mmol persistently • excessive dose of sitagliptin • aspirin > 150 mg/day for an older adult • low dose carvedilol for dilated cardiomyopathy • simvastatin at more than 20 mg while receiving amlodipine • without considering dosage reduction for older adults |
Drug-drug interaction
| • aspirin + lisinopril/enalapril/glibenclamide/insulin/clopidogrel/coumadin/ACEIs/ enoxaparin/ketorolac/enoxaparin/lornoxicam/diclofenac/piroxicam/heparin/ glimepiride/NSAID/simvastatin/furosemide/SSRI/metimazole/warfarin/glipizide • metformin + ciprofloxacin/cimetidine/atenolol/enalapril/carvedilol/ranitidine/ salbutamol/furosemide/clarithromycin/spironolactone/levothyroxine/moxifloxacin/ nifedipine/aspirin/captopril/HCT/simvastatin/paracetamol/budesonide • insulin + metformin/aspirin/ciprofloxacin/moxifloxacin/bisoprolol/losartan/ enalapril/carvedilol/captopril/atenolol/thiazide/timolol/levofloxacin/metoprolol/ ACEIs • simvastatin + macrolide antibiotics/ketoconazole/itraconazole/amlodipine/ fenofibrate/warfarin/amlodipine/diltiazem/phenofibrate/verapamil • glimepiride + aspirin/salbutamol/metoprolol/fluconazole/ramipril/sitagliptin/ bisoprolol/ibuprofen/furosemide/losartan/ciprofloxacine/budesonide/warfarin/ lisinopril • atorvastatin + macrolide antibiotics/ketoconazole/itraconazole/macrolide antibiotic/ simvastatin/rosuvastatin/clopidogrel/sitagliptin • duloxetine + metoclopramide/aspirin/ciprofloxacin/anticoagulants/antiplatelet drugs/ NSAIDs/tramadol/metoclopramide • glibenclamide + diclofenac/ranitidine/hydrocortisone/simvastatin/antacid/ topiramate • digoxin + HCT/verapamil/amiodarone/warfarin/furosemide/atorvastatin/ spironolactone • atenolol + amlodipine/gliclazide/glibenclamide/verapamil/carvedilol/clonidine • amiodarone + amlodipine/atenolol/amitriptyline/fluoxetine/digoxin/nepheline • fluoxetine + amitriptyline/haloperidol/diclofenac • glipizide + warfarin/ciprofloxacin/enalapril • pregabalin + naproxen/enalapril/captopril • lisinopril + furosemide/KCl • pioglitazone + insulin glargine/ciprofloxacin • sulfonylureas + trimethoprim/sulfamethoxazole/ACEIs/CYP2C9-inhibitors/anti-hyperlipidaemic • antidiabetics + diuretics/ACEI/anti-lipidaemic drugs/corticoids/other drugs that have a hypoglycaemic effect/β-blockers • CCBs + β-blockers/clopidogrel • thiazide diuretic + ACEIs/ARBs + NSAIDs • NSAIDs + ACEIs/ARBs/β-blockers/spironolactone; ACEIs + ARBs • losartan + spironolactone; pravastatin + darunavir; repaglinide + brotizolam; enalapril + losartan; furosemide + gentamicin; nifedipine + erythromycin; HCT + carbamazepine |
Inappropriate drug selection
|
Prescribing –
• antidiabetic other than metformin as an initial therapy for T2DM • only glibenclamide for an obese DM patient • combined oral therapy without starting with monotherapy • insulin for a patient who need tablet treatment • incorrect insulin type, insulin glargine instead of insulin detemir • monotherapy with long-acting insulin, rapid-acting insulin, or GLP-1 agonist • improper combination of short-, intermediate-, or long-acting insulin • non-statin therapy in a statin-eligible patient • inappropriate intensity statin/low-intensity statin in a high CVD risk patient • non-recommended dual therapy, or triple therapy (add-on therapy to insulin, insulin + metformin, or α-blockers such as prazosin and doxazosin as second or third add-on therapies when other better alternatives were available and not contraindicated) • unadjusted antidiabetic drug while HbA1c value is higher or lower than the patient’s target range • spironolactone and furosemide while thiazide-like diuretic is preferred • CCBs (e.g. amlodipine) instead of ACEIs/ARBs for HTN treatment • drug was fragmented despite being a special oral formulation |
Unnecessary drug therapy
|
Prescribing –
• antiplatelet (e.g. aspirin) or statin for illegible individuals • intensified antidiabetic medication for a patient with limited life expectancy or already at goal HbA1c • dual antihypertensive agents for a stage I hypertensive patient • loop diuretics in the absence of clinical signs of HF • aspirin to a patient with cardiovascular and/or coronary risk < 1.0 event/100 patients/year |
Prevalence of potentially inappropriate prescribing
Types of PIP | Percentage calculated from | Number of studies reported | Range of reported prevalence | Median prevalence | IQR |
---|---|---|---|---|---|
Contraindication
| Adults with DM | 41 | 1.0 − 93.4% | 21.6% | 8.0 − 34.9% |
DRPs identified | 9 | 0.3 − 7.5% | 1.4% | 0.8 − 4.3% | |
Dosing problem
| Adults with DM | 26 | 2.4 − 63.0% | 12.5% | 6.2 − 27.8% |
DRPs identified | 19 | 4.0 − 49.3% | 17.9% | 12.7 − 37.8% | |
Drug-drug interaction
| Adults with DM | 24 | 4.0 − 96.0% | 45.1% | 17.4 − 61.4% |
DRPs identified | 12 | 0.4 − 18.2% | 9.1% | 1.0 − 17.6% | |
Inappropriate drug selection
| Adults with DM | 13 | 3.1 − 90.6% | 13.3% | 8.0 − 37.0% |
DRPs identified | 16 | 1.0 − 37.0% | 10.7% | 3.3 − 21.7% | |
Prescribing omission
| Adults with DM | 29 | 2.9 − 91.2% | 26.7% | 16.3 − 54.9% |
DRPs identified | 21 | 2.0 − 49.3% | 19.1% | 9.7 − 26.2% | |
Unnecessary drug therapy
| Adults with DM | 10 | 1.0 − 43.0% | 14.1% | 2.7 − 27.9% |
DRPs identified | 18 | 0.7 − 29.7% | 8.8% | 4.0 − 17.2% |
Identified gaps regarding PIP for adults with DM
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PIP is less studied in low- and middle-income countries (LMICs) where the risk of PIP could be high due to less efficient systems and resource scarcities.
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PIP is less studied in nursing home and community dwelling adults living with DM.
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The specific events and conditions that were considered as inappropriate prescribing were inconsistent across included studies.
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There are no explicit tools/criteria solely designed to identify PIP among adults with DM.