If glycaemic targets are not achieved, diabetes is associated with a high number of health complications, which are burdensome for both the individual and society. |
Lack of adherence and persistence to basal insulin treatment is one cause of poor glycaemic control. In order to support people with diabetes achieving adherence and persistence, it is important first to understand the scope of the problem. |
Twelve eligible studies presenting estimates of basal insulin adherence/non-adherence and/or persistence/non-persistence in people with type 2 diabetes (T2D) in Western European countries were identified. |
The findings suggest that approximately 20%, 34% and 37% of people with T2D are non-persistent to basal insulin within 6, 12 and 18 months of initiation of treatment, respectively. Additionally, 44% are non-adherent to basal insulin treatment within 12 months. |
The findings of the present systematic literature review highlight a huge unmet need in the care for people with T2D and indicate that there is a clear opportunity to improve adherence and persistence. |
Introduction
Methods
Database | Search string | ||||
---|---|---|---|---|---|
Diabetes | AND | Outcomes | AND | Insulin | |
Medline | “Diabetes Mellitus”[Mesh] OR “Diabetes Mellitus, Type 2”[Mesh] OR “Diabetes Mellitus, Type 1”[Mesh] OR diabetes[Title/Abstract] OR diabetic[Title/Abstract] OR diabetics[Title/Abstract] NOT “pre-diabetes” OR “pre diabetes” OR “pregnancy induced diabetes” OR “gestational diabetes” OR “diabetes insipidus” | “Adherance” OR “adhere” OR “adhered” OR “adherence” OR “adherences” OR “adherent” OR “adherents” OR “adherer” OR “adherers” OR “adheres” OR “adhering” OR “persist” OR “persistance” OR “persistant” OR “persisted” OR “persistence” OR “persistences” OR “persistencies” OR “persistency” OR “persistent” OR “persistently” OR “persistents” OR “persister” OR “persisters” OR “persisting” OR “persists” | Insulin[Title/Abstract] AND “Insulin glargine” OR Lantus OR Toujeo OR Basaglar OR Semglee OR “Insulin detemir” OR Levemir OR “Insulin degludec” OR Tresiba OR “Basal insulin” OR “background insulin” OR “Intermediate-acting insulin” OR “Long-acting insulin” OR “Ultra-long acting insulin” OR NPH OR “neutral protamine Hagedorn” | ||
Embase | Exp diabetes mellitus/OR exp insulin dependent diabetes mellitus/OR exp non insulin dependent diabetes mellitus/ AND diabetes.ti,ab. OR diabetic.ti,ab. OR diabetics.ti,ab NOT pre-diabetes.mp. OR pre diabetes.mp. OR pregnancy induced diabetes.mp. OR gestational diabetes.mp. OR diabetes insipidus.mp | (Adherance OR adhere OR adhered OR adherence OR adherences OR adherent OR adherents OR adherer OR adherers OR adheres OR adhering OR persist OR persistance OR persistant OR persisted OR persistence OR persistences OR persistencies OR persistency OR persistent OR persistently OR persistents OR persister OR persisters OR persisting OR persists).mp | Insulin.ti,ab AND (Insulin glargine OR Lantus OR Toujeo OR Basaglar OR Semglee OR Insulin detemir OR Levemir OR Insulin degludec OR Tresiba OR Basal insulin OR background insulin OR Intermediate-acting insulin OR Long-acting insulin OR Ultra-long acting insulin OR NPH OR neutral protamine hagedorn).mp |
Eligibility Criteria
Inclusion | Exclusion | |
---|---|---|
Population | Adults with diabetes | Pre-diabetes, gestational diabetes, diabetes insipidus Children and adolescents Not diabetes Not humans |
Intervention | Basal insulin such as insulin glargine, Lantus, Toujeo, Basaglar, Semglee, insulin detemir, Levemir, insulin degludec, Tresiba, NPH, neutral protamine Hagedorn, background insulin, intermediate-acting insulin, long-acting insulin and ultra-long-acting insulin | Bolus insulin such as insulin lispro, insulin glulisine, insulin aspart, Humulin, Novolin, Novolog, Humalog mix, rapid-acting and short-acting. Pre-mix insulin |
Comparator | Not relevant | Not relevant |
Outcomes | Proportions related to adherence or persistence to basal insulin treatment | Adherence of devices to support insulin usage (such as an app, patient education programmes etc.) or treatments other than basal insulin |
Study type | Original data sources/analyses (such as observational studies, questionnaires, clinical trials) Aggregated population data | Reviews, systematic reviews, meta-analysis Commentaries, editorial letters, case studies, case series, case report, abstracts and conference posters Individual patient data In vivo or in vitro |
Language | English | Other languages |
Time limit | Published within the last 10 years | Published prior to 2012 |
Countries | Results should be presented on country level. Including countries from Western Europe, including the UK, France, Spain, Switzerland, Netherlands, Ireland, Austria, Portugal, Denmark, Norway, Sweden, Finland, Italy, Germany, Iceland and Belgium | All other countries |
Study Selection and Data Collection
Identified Studies
Data Extraction and Statistical Analyses
Results
Identified Outcome Measures
Identified outcome measures | No. |
---|---|
Persistence | |
Persistence after 24 months (%) | 8 |
Persistence after 18 months (%) | 2 |
Persistence after 12 months (%) | 8 |
Persistence after 6 months (%) | 7† |
Persistence after 3 months (%) | 1 |
Adherence | |
MPR after 12 months | 1 |
Share with MPR > 80% (%) | 4 |
Share with MPR 50–79% (%) | 1 |
Share with MPR < 50% (%) | 1 |
Share with missed doses (%) | 3 |
Mean number of missed doses | 3 |
Share with 5+ missed doses within 30 days (%) | 3 |
Share with mistimed doses (%) | 3 |
Mean number of mistimed doses | 3 |
Share with 5+ mistimed doses within 30 days (%) | 3 |
Share with reduced doses (%) | 3 |
Mean number of reduced doses | 3 |
Share with 5+ reduced doses within 30 days (%) | 3 |
Share that are adherent all 7 days within a week (%) | 1 |
Results on Insulin Persistence
Author and year | Country | Study type and data source | Follow-up | Type of basal insulin | Population size | Age, mean (SD) | Background therapy (%) | Diabetes duration | Complications associated with diabetics | Outcome measure | |
---|---|---|---|---|---|---|---|---|---|---|---|
Eliasson et al. 2020 [31] | Sweden | Cohort study with registry data | 12 months | Degludec | N = 2432 | 61.3 (11.8) | Liraglutide | 12.7 (7.6) years | Microalbuminuria: 30.51% Macroalbuminuria: 9.04% Retinopathy: 41.85% | Persistence after 6 months: 94% Persistence after 12 months: 84% | |
Perez-Nieves et al. 2017 [9] | UK, Germany, France, Spain | Cross-sectional study with questionnaire data | 24 months | Glargine, detemir or degludec | N = 549 UK: n = 131 Germany: n = 131 France: n = 137 Spain: n = 150 | Total: 40.6 (14.1)† | Antihyperglycaemic medication: 65.5 (Oral: 57.7, Injectable: 24.1) | Total: 6.8 (7.0) years† | NR | Persistence after 6 months UK: 24% Germany: 20% France: 27% Spain: 33.3% | |
Pscherer et al. 2014 [33] | Germany | Cohort study with registry data | 24 months | Glargine, detemir or NPH | N = 5736 Glargine‡: n = 1398 Detemir‡: n = 292 NPH‡: n = 874 Glargine§: n = 866 Detemir§: n = 512 NPH§: n = 1794 | Total: NR Glargine‡: 67.7 (11.3) Detemir‡: 66 .4 (11.4) NPH‡: 65 (11.1) Glargine§: 63.8 (12.8) Detemir§: 60.4 (12.9) NPH§: 63.9 (11.9) | Antihypertensive drugs Glargine‡: 80.3 Detemir‡: 81.5 NPH‡: 73.8 Glargine§: 65.6 Detemir§: 57.8 NPH§: 64.9 | Lipid-lowering drugs Glargine‡: 44.6 Detemir‡: 48.6 NPH‡: 45.5 Glargine§: 37.6 Detemir§: 40.4 NPH§: 38.9 | > 5 years Glargine‡: 44.0% Detemir‡: 48.6% NPH‡: 35.6% Glargine§: 32.3% Detemir§: 26.6% NPH§: 30.2% | Diagnosed co-morbidity (% for glargine, detemir, NPH) Coronary heart disease: 26.8, 25.7, 24.9 Myocardial infarction: 4.7, 4.5, 4.5 Stroke: 8.8, 7.2, 6.8 Peripheral vascular disease: 12.5, 17.8, 13.4 Heart failure: 18.8, 14.7, 14.0 Hypertension: 75.3, 80.8, 72.4 Hyperlipidemia: 51.8, 52.7, 53.4 Retinopathy: 5.4, 7.9, 5.6 Nephropathy: 13.9, 11.0, 12.0 Neuropathy: 14.5, 16.8, 19.7 | Persistence after 24 months Glargine‡: 64.5% Detemir‡: 52.7% NPH‡: 59.2% Glargine§: 84.3% Detemir§: 85.4% NPH§: 86.6% |
Quinzler et al. 2012 [34] | Germany | Cohort study with registry data | 12 months | Glargine or NPH | N = 97,998 Glargine: n = 61,070 NPH: n = 36,928 | NR | Metformin + OAD Glargine: 65.6 NPH: 66.6 Metformin only Glargine: 8.0 NPH: 12.2 | Sulfonylurea Glargine: 16.8 NPH: 13.1 Other OAD Glargine: 9.7 NPH: 8.1 | NR | NR | Persistence after 12 months Glargine: 42.4% NPH: 36.8% |
Rathmann et al. 2017 [16] | Germany | Cohort with registry data | 24 months | NPH, glargine or detemir | N = 680,131 NPH: n = 226,064 Glargine/detemir: n = 454,067 | Total: NR NPH: 68.1 (11.3) Glargine/detemir: 67.7 (12.2) | Antidepressants NPH: 17.2 Glargine/detemir: 19.5 Antihypertensives NPH: 83.3 Glargine/detemir: 82.5 | Antiepileptics NPH: 12.0 Glargine/detemir: 13.1 Lipid-lowering drugs NPH: 49.2 Glargine/detemir: 49.0 | NR | NR | Persistence after 24 months NPH: 79% Glargine/detemir: 92.6% |
Roussel et al. 2016 [36] | France | Cohort study with registry data | 24 months | NR | N = 1199 | 67.5 (14.2) | Insulin + 1 OAD: 23.0 Insulin + 2 OAD: 31.6 Insulin + 3 OAD: 24.9 Insulin ≥ 4 OAD: 1.6 Metformin: 59.6 | Sulfonylurea: 44.6 Glinides: 17.9 Alpha-glucosidase inhibitor: 3.5 GLP-1 receptor agonists: 10.6 DPP4 inhibitor: 31.4 | NR | NR | Persistence after 6 months: 80.9% Persistence after 12 months: 71.3% |
Roussel et al. 2020 [35] | France | Cohort study with registry data | 24 months | Glargine-300, glargine-100 or detemir | N = 181,263 Glargine-100: n = 134,127 Glargine-300: n = 21,306 Detemir: n = 25,830 | All: NR Glargine-100: 67.5 (15.6) Glargine-300: 64.8 (14.3) Detemir: 67 (16.9) | OAD Glargine-100: 57.9 Glargine-300: 60.9 Detemir: 53.8 GLP-1 RA + OAD Glargine-100: 7.1 Glargine-300: 14.2 Detemir: 13.8 | Other insulins + OAD Glargine-100: 33.1 Glargine-300: 21.8 Detemir: 30.1 Other insulin + GLP-1 RA + OAD Glargine-100: 1.9 Glargine-300: 3.1 Detemir: 2.4 | All: NR Glargine-100: 8.5 (7.2) years Glargine-300: 8.4 (6.7) years Detemir: 9 (7.2) years | Charlson Comorbidity index (% for glargine-100, glargine-300, detemir) 0: 39.78, 32.88, 29.87 1: 21.48, 18.24, 20.07 2: 14.01. 14.16, 14.50 3: 8.86, 10.65, 10.94 4: 5.76, 7.76, 7.81 5: 3.70. 5.49, 5.52 6: 2.18, 3.28, 3.41 7 or more: 4.23, 7.54, 7.88 | Persistence after 12 months: 72% Glargine-100: 66% Glargine-300: 86% Detemir: 63% |
Sicras et al. 2013 [37] | Spain | Cohort study with registry data | 12 months | NR | N = 935 | 67.6 | NR | NR | NR | Persistence after 3 months: 90.3% Persistence after 6 months: 79.4% Persistence after 12 months: 55.9% | |
Westerbacka et al. 2015 [25] | Finland | Cohort study with registry data | 18 months | Glargine or detemir | N = 14,462 Glargine: n = 8594 Detemir: n = 5868 | NR | NR | NR | NR | Persistence after 18 months Glargine: 65% Detemir: 62% |
Results on Insulin Adherence
Author and year | Country | Study type and data source | Follow-up | Type of basal insulin | Population size | Age, mean (SD) | Background therapy (%) | Diabetes duration | Complications associated with diabetics | Outcome measure |
---|---|---|---|---|---|---|---|---|---|---|
Brod et al. 2012 [30] | UK, Germany, Denmark | Cross-sectional study with questionnaire data | 1 month | NR | N = 681 UK: n = 322 Germany: n = 302 Denmark: n = 57 | All: NR UK: 60 (8.63) Germany: 57 (7.75) Denmark: 62 (8.27) | NR | All: NR UK: 11 years (6.45) Germany: 9 years (5.94) Denmark: 11.7 years (6.47) | Number of diabetes complications (median (range)) UK: 3 (0–10) Germany: 3 (0–9) Denmark: 3 (0–8) | % of people with missed, mistimed and reduced doses UK: 16%, 20%, 18% Germany: 19%, 25%, 15% Denmark: 12%, 20%, 12% % of people with 5+ missed, mistimed and reduced doses UK: 1.6%, 4.3%, 3.5% Germany: 2.2%, 6.3%, 5% Denmark: 0%, 6%, 0% Mean number of missed, mistimed and reduced doses UK: 2.1, 3.7, 3.8 Germany: 2.3, 3.9, 5.3 Denmark: 1.1, 3.7, 1.3 |
Esposti et al. 2019 [32] | Italy | Cohort study with registry data | 12 months | Glargine-100 | N = 2413 Insulin only: n = 466 OGLD: n = 1590 DPP4 inhibitor: n = 357 | All: NR Insulin only: 71.7 (14.6) OGLD: 71.8 (11.9) DPP4 inhibitor: 67.7 (10) | OGLD or DPP4 inhibitor | NR | % reported for insulin only, OGLD, DPP4 inhibitor Hypertension: 65.0, 75.6, 77.0 Dyslipidemia: 32.8, 50.6, 60.2 Anti-inflammatory agents: 14.4, 18.1, 17.4 Asthma/COPD: 10.3, 9.7, 6.2 Kidney disease: 8.6, 3.4, 3.4 Hypoglycaemia: 0.6, 0.7, 1.4 Previous CV events: 28.3, 14.6, 10.9 Hypertensive disease: 14.4, 9.2, 7.0 Acute myocardial infarction: 2.4, 1.1, 0.8 Coronary disease: 8.2, 4.0, 6.4 Heart failure: 7.7, 3.5, 2.2 Stroke and other cerebral circulatory dysfunction: 11.4, 5.0, 1.7 Arteriosclerosis of the main arteries and aneurysm: 1.7, 1.8, 1.4 | % of people with MPR > 80% Insulin only: 41% OGLD: 61.9% DPP4 inhibitor: 64.4% |
Sicras et al. 2013 [37] | Spain | Cohort study with registry data | 12 months | NR | N = 935 | 67.6 | NR | NR | NR | MPR after 12 months: 82.7% % of people with MPR > 80%: 54.7% % of people with MPR 50–79%: 39.9% % of people with < 50%: 5.5% |
Wieringa et al. 2018 [15] | Netherlands | Cohort study with questionnaire data | 6 months | Glargine-300 | N = 162 | 65.54 (9.05) | NR | 15.14 years (6.65) | Ongoing complications and/or comorbidities at baseline 0: 34.2% 1: 28.4% 2: 23.9% 3 or more: 13.5% | % of patients adherent all 7 days within a week: 84.4% |