Table 1 Summary of previous studies on adherence and persistence of major antidiabetic medications

Metformin

Horsburgh et al., 2021 [26]

The Ministry of Health’s Virtual Diabetes Register (VDR)

N.A

Having a gap of ≥ 90 days

85,066 T2DM patients aged 18 or older in New Zealand who initiated monotherapy between January 1st 2006 and September 30^th 2014

1 year to 5 year

At year 1 after cohort entry, 28.2% of cohort members had discontinued metformin monotherapy at least once and 62.8% remained persistent; at year 2, 36.8% had discontinued at least once and 48.5% remained persistent; at year 5, 46.3% discontinued at least once and 27.7% remained persistent

Flory et al., 2017 [7]

The OptumLabs Data Warehouse (OLDW)

Daily medication possession probability (daily MPP)

N.A

11,067 T2DM patients aged 18 or older (37.2% metformin users) who received a first electronic prescription for one of the index medications during the 2012 calendar year

1 year

The daily MPP of metformin-prescribed patients during one year of follow-up was 0.46

Flory et al., 2018 [28]

The Weill Cornell Medicine Database

N.A

Absence of any further metformin prescriptions after the first 90 days

1,259 treatment-naïve T2DM patients who initiated metformin therapy between January 1st 2009 and September 31st 2015

 > 1.5 year

The overall rate of early discontinuation was 20.3%

Naffaa et al., 2020 [84]

Maccabi Healthcare Services

Proportion of days covered (PDC)

N.A

113,749 T2DM patients aged 18 or older in Israel who initiated metformin between 1998 and 2014

1 year

30.8% of patients demonstrated adherence (PDC ≥ 0.8)

Walker et al., 2020 [85]

Diabetes Prevention Program Outcomes Study (DPPOS) Follow-up Data

Percentage of pill taken

N.A

664 T2DM patients who were enrolled in Diabetes Prevention Program (DPP) and had taken adherence assessment semiannually

11 years

Overall the cumulative adherence in 11 years was 60%

Nishimura et al., 2019 [27]

The Japan Medical Data Center (JMDC) database and the Medical Data Vision (MDV) database

Proportion of days covered (PDC)

Percentage of patients who remained on treatment after one-year follow-up

40,908 and 90,421 (from JMDC and MDV, respectively) adult T2DM patients aged 18 or older in Japan during January 2011 to December 2015

1 year

Twelve-month persistence to metformin was 57.3% and 73.8% for treatment naïve patients identified from JMDC and MDV, respectively; twelve-month persistence was 69.3% and 73.6% for previously treated patients identified from JMDC and MDV; the corresponding twelve-month adherence was 0.86, 0.97, 0.83, and 0.95

Sulfonylureas

Bell et al., 2017 [31]

The Truven Health Market-Scan®; Commercial Claims and Encounters; Medicare Supplemental and Coordination of Benefits; Early View databases

Proportion of days covered (PDC)

The number of days from the index date until the earlier of a discontinuation of the index medication class or the end of follow-up

25,490 T2DM patients (aged 18 and above) with at least 1 outpatient pharmacy claims for sulfonylurea between January 1, 2015 and December 31, 2015

6 months

The average PDC was 0.72; the proportion of adherent patients (with PDC ≥ 0.8) was 53.9%; 31.1% of the patients discontinued (not persistent)

Popoviciu et al., 2019 [38]

Clinical charts, laboratory parameters reviews, and cross-sectional survey data in Romania

Patient-report questionnaire

N.A

385 T2DM patients (30 years of age or older) who have been taking sulfonylureas (monotherapy or in combination therapy with metformin) for at least 6 months prior to enrollment

2 months

77% of patients adhered to their prescriptions every day

Bloomgarden et al., 2017 [32]

MarketScan® Commercial Claims and Encounters; Medicare Supplemental databases;

Truven Health Analytics

Proportion of days covered (PDC)

The proportion of patients who continued to use their index medications

34,113 T2DM patients aged 18 years or older who initiated either sitagliptin or sulfonylurea as an add-on to metformin from January 1, 2009 to December 31, 2012

1 to 3 years

55.9% of patients on metformin and sulfonylurea were adherent (PDC ≥ 0.8) at Year 1; 49.9% remained adherent at Year 2; 47.1% remained adherent at Year 3; the adherence of patients on metformin and sitagliptin was higher than that of patients on metformin and sulfonylurea (p < 0.001); the median time of discontinuation for patients on metformin and sitagliptin was 133 days longer

Carls et al., 2017 [36]

The Optum/Humedica SmartFile Database

Proportion of days covered (PDC)

Absence of a 30-day gap in medications on hand without subsequent fills

5,818 T2DM patients aged 18 years or older who initiated the index medication between January 2007 and December 2014 (2,713 sulfonylurea users)

1 year

The average PDC was 0.62; 40% of patients showed good adherence (PDC ≥ 0.8); 38% of patients discontinued before the end of follow-up

McGovern et al., 2018 [1]

The Royal College of General Practitioners Research and Surveillance Centre (RCGP-RSC) database

N.A

Absence of a gap in prescriptions of greater than or equal to 90 days; the duration of persistence was defined as the time interval between the first prescription and the last identified prescription

60,327 T2DM patients who initiated treatment with one of the index medications between January 1, 2005 and December 31, 2015 (20,819 sulfonylurea users)

6 months, 1 year, 2 years, and 5 years

The median duration of persistence of patients treated with sulfonylureas was 2.12 years; 76.6% of patients remained persistent at 6 months; at 1 year, 64.8% remained persistent; at 2 years, 51.3% remained persistent; at 5 years, 31.6% remained persistent; the hazard ratio (HR) of discontinuation of sulfonylureas to that of metformin via Cox regression analysis was 1.2 (95% CI 1.16 to 1.24, p < 0.001)

Nishimura et al., 2019 [27]

The Japan Medical Data Center (JMDC) database and the Medical Data Vision (MDV) database

Proportion of days covered (PDC)

Percentage of patients who remained on treatment after one-year follow-up

40,908 and 90,421 (from JMDC and MDV, respectively) adult T2DM patients aged 18 or older in Japan who had been issued at least one prescription for the index medication during January 2011 to December 2015

1 year

Twelve-month persistence rates were 50.4% and 56.0% for treatment naïve patients identified from JMDC and MDV, respectively; twelve-month persistence rates were 58.1% and 62.2% for previously treated patients identified from JMDC and MDV; twelve-month adherence was 0.86 and 0.96 for treatment naive patients identified from JMDC and MDV; twelve-month adherence was 0.85 and 0.97 for previously treated patients identified from JMDC and MDV respectively

SGLT2 inhibitors

Cai et al., 2017 [41]

The QuintilesIMS PharMetrics Plus Health Plan Claims Database

Proportion of days covered (PDC); medication possession ratio (MPR)

The number of consecutive days until discontinuation or end of follow-up (discontinuation was defined as having ≥ 90 days of prescription gap)

23,720 T2DM patients aged 18 or older with at least 1 pharmacy claims for an index medication between February 1, 2014 and June 30, 2014 (6,546 canagliflozin users, 3,087 dapagliflozin users)

1 year

Mean PDC for canagliflozin was 0.71, and the proportion of adherent patients (PDC ≥ 0.8) were 56.2%; mean persistence for canagliflozin was 278.6 days; the proportion of patients who remained on canagliflozin therapy was 67.6%; mean PDC for dapagliflozin was 0.64, and the proportion of adherent patients (PDC ≥ 0.8) was 41.8%; mean persistence for dapagliflozin was 260.3 days; the proportion of patients who remained on dapagliflozin therapy was 57.4%

Fadini et al., 2019 [49]

The DARWIN (DApagliflozin Real World evidence)-T2D study

N.A

The presence of prescription for the index medication at the first available visit 3–12 months after treatment initiation

12,782 T2DM patients (aged 18 to 80) who have initiated dapagliflozin 10 mg as add-on to metformin and/or insulin from March 13, 2015 to December 31st, 2016 (1,701 dapagliflozin users)

1 year

48.9% of patients remained persistent; adjusted for covariates, the relative risk of discontinuation associated with dapagliflozin versus other antidiabetic medications was 1.32 (95% CI 1.17- 1.47, p < 0.001)

Thayer et al., 2017 [45]

The Optum Research Database

N.A

The number of days without a prescription gap of ≥ 90 days

2944 T2DM patients aged 18 years or older with at least 1 pharmacy claim for canagliflozin or sitagliptin between April 1, 2013 and December 31, 2013

9 months

29% of patients on canagliflozin discontinued while 41.5% of patients on sitagliptin discontinued (p < 0.001); the average days of persistent treatment with canagliflozin was longer than the average days of persistent treatment with sitagliptin (152 days vs. 139 days; p < 0.001)

McGovern et al., 2018 [2]

The Royal College of General Practitioners Research and Surveillance Centre (RCGP-RSC) database

N.A

Absence of a gap in prescriptions of greater than or equal to 90 days

the duration of persistence was defined as the time interval between the first prescription and the last identified prescription

60,327 T2DM patients who initiated treatment with one of the index medications between January 1, 2005 and December 31, 2015 (1642 SGLT2 inhibitor users)

6 months, 1 year, 2 years, and 5 years

79.5% of patients remained persistent at 6 months; at 1 year, 69.5% remained persistent; at 2 years, 54.8% remained persistent; the hazard ratio (HR) of discontinuation of SGLT2 inhibitors to that of metformin via Cox regression analysis was 1.04 (95% CI 0.93–1.17, p = 0.458)

Tumminia et al., 2020 [48]

Electronic chart records from Diabetes Center at the Garibaldi Hospital (Catania, Italy)

N.A

Discontinuation rate (i.e., the proportion of patients who didn't continue treatment until the end of follow-up)

364 T2DM patients aged 65 years or older, who started treatment with SGLT2 inhibitor from June 2015 to June 2018

2 years

Discontinuation rate in patients aged between 65 and 70 was 34.2%; discontinuation rate in patients aged 70 or older was 36.1%; there was no significant group difference in discontinuation rate (p = 0.26)

Ito et al., 2019 [43]

The Japan Medical Data Center (JMDC) database and the Medical Data Vision (MDV) database

N.A

Percentage of patients who remained on treatment after one-year follow-up

1,641 T2DM patients aged 18 or older with at least 1 prescription record of SGLT2 inhibitor between April 1, 2014 and March 31, 2016

1 year

44.3% of patients from JMDC were persistent; 53.3% of patients from MDV were persistent

Ofori-Asenso et al., 2019 [42]

The National Pharmaceutical Benefits Scheme of Australia

Proportion of days covered (PDC)

Continuous use of SGLT2 inhibitors without a prescription gap of ≥ 90 days

11,981 T2DM patients (aged 18 and above) who newly initiated treatment with dapagliflozin or empagliflozin from September 2015 to August 2017 (5993 dapagliflozin users, 5988 empagliflozin users)

1 year

Mean PDC for both SGLT2 inhibitors was 0.79; 65.8% of patients treated with SGLT2 inhibitors were adherent (PDC ≥ 0.8); 72.1% (8644/11981) were persistent at 1 year; the use of empagliflozin was associated with being adherent and persistent than the use of dapagliflozin (OR 1.39, 95% CI 1.29 to 1.51 and OR 1.14, 95% CI 1.06–1.22, respectively)

Nishimura et al., 2019 [27]

The Japan Medical Data Center (JMDC) database and the Medical Data Vision (MDV) database

Proportion of days covered (PDC)

Percentage of patients who remained on treatment after one-year follow-up

40,908 and 90,421 (from JMDC and MDV, respectively) adult T2DM patients aged 18 or older in Japan who had been issued at least one prescription for the index medication during January 2011 to December 2015

1 year

Twelve-month persistence rates were 53.5% and 63.4% for treatment naïve patients identified from JMDC and MDV, respectively; twelve-month persistence rates were 62.8% and 66.4% for previously treated patients identified from JMDC and MDV; twelve-month adherence was 0.75 and 0.95 for treatment naive patients identified from JMDC and MDV; twelve-month adherence was 0.77 and 0.92 for previously treated patients identified from JMDC and MDV respectively

DPP4 inhibitors

Rascati et al., 2017 [56]

Humana's administrative claims database

Proportion of days covered (PDC)

The number of days on an index medication before a gap in therapy of greater than 31 days

26,089 T2DM patients aged 18 or older with a prescription claim between July 1, 2011 and March 31, 2013, who were enrolled in a Medicare Advantage Prescription Drug (MAPD) plan or a commercial insurance plan

1 year

MAPD patients on sitagliptin, saxagliptin, and linagliptin showed mean one-year PDC of 0.72, 0.72, and 0.67, respectively; the percentages of adherent patients (PDC ≥ 0.8) were 49.9%, 50.9%, and 41.4% for sitagliptin, saxagliptin, and linagliptin; the percentages of discontinuation patients for sitagliptin, saxagliptin, and linagliptin were 66.5%, 64.7%, and 72.6%

Oh et al., 2019 [59]

The Medical Data Vision (MDV) database

Proportion of days covered (PDC)

The percentage of patients who continued treatment over one-year period

39,826 T2DM patients (aged 18 or older with a prescription claim between May 2015 and May 2018; 15,435 patients were treatment naïve, while 24,391 patients had previous treatment histories

1 year

Regardless of treatment history, adherence and persistence to the once-daily regimen was slightly higher than that of twice-daily regimen (p = 0.1187), while significantly higher than that of once-weekly regimen (p < 0.0001)

Moura et al., 2018 [86]

The MarketScan® commercial claims and encounters database

N.A

The number of days without a prescription gap of ≥ 90 days

54,318 T2DM patients aged 18 years or older newly dispensed with either NPH insulin or a DPP4 inhibitor as an add-on to metformin and sulfonylurea between January 2011 and December 2014 (50,338 DPP4 users)

1 year

Cox regression analysis results showed that HR of discontinuation for NPH insulin was 1.33 compared with DPP4 inhibitors (95% CI 1.27–1.40, p < 0.05), when adjusted for baseline patient characteristics

McGovern et al., 2018 [2]

The Royal College of General Practitioners Research and Surveillance Centre (RCGP-RSC) database

N.A

Absence of a gap in prescriptions of ≥ 90 days

60,327 T2DM patients who initiated treatment with one of the index medications between January 1, 2005 and December 31, 2015 (9614 DPP4 inhibitor users)

6 months, 1 year, 2 years, and 5 years

Median persistence was 1.69 years; percentages of persistent patients at 6 months, 1 year, 2 years, and 5 years were 76.1%, 62.2%, 45.5%, and 23.0%, respectively; HR of discontinuation for DPP4 inhibitors compared with metformin was 1.43 (95% CI 1.38–1.49, p < 0.001)

Ogundipe et al., 2021 [61]

Systematic review and meta-analysis

Proportion of days covered (PDC); medication possession ratio (MPR)

The number of days without a prescription gap of ≥ 90 days

Pooled analysis on 594,138 T2DM patients (aged 18 or older) identified in 34 studies

6 months, 1 year, 2 years, 3 year

The pooled estimate for PDC (and MPR) was 0.72 (95% CI 0.68 to 0.77, I² = 99.5%); the pooled estimate for the percentage of adherent patients (PDC ≥ 0.8) was 56.9% (95% CI 49.3–64.4%, I² = 99.9%); the pooled estimates for the percentages of persistent patients at six months, one year, two years, and three years were 75.6% (95% CI 71.5–79.5%, I² = 99.8%), 60.0% (95% CI 57.0–62.0%, I² = 99.8%), 52.8% (95% CI 51.6–59.8%, I² = 99.8%), and 31.4% (95% CI 31.0–31.8%, I² = 0%)

Kadowaki et al., 2018 [58]

The Medical Data Vision (MDV) database

N.A

The number of days without a prescription gap of ≥ 30 days

162,116 T2DM patients aged 40 or older with at least 1 prescription record of antidiabetic medication between January 1, 2014 and September 30, 2016

N.A

Besides metformin, treatment persistence was longest for DPP4 inhibitors (median 17.0 [95% CI 16.4–17.5] months); Persistence was longest with DPP4 inhibitors at all renal impairment stages (G1 to G4 +)

Ito et al., 2019 [60]

Prospective study by the Department of Diabetes, Metabolism and Kidney Disease, Edogawa Hospital (Tokyo, Japan)

The Diabetes Treatment Satisfaction Questionnaire (DTSQ)

N.A

79 T2DM patients aged 18 or older who switched treatment from daily DPP4 inhibitors to once-weekly trelagliptin between January 2017 to March 2018

3 months

The scores representing treatment satisfaction and medication adherence improved after switching from daily DPP-4 inhibitors to once-weekly trelagliptin (p < 0.01)

Gor et al., 2020 [57]

The MarketScan® commercial claims and encounters database

Proportion of days covered (PDC)

The number of days before the gap of two times the day’s supply or the end of follow-up

9,019 T2DM patients (aged 18 and above) with non-dialysis chronic kidney disease, who initiated either a DPP4 inhibitor or pioglitazone (7,002 DPP4 inhibitor users)

1 year

Mean one-year PDC for DPP4 inhibitors was 0.77 while mean PDC for pioglitazone was 0.72 (p < 0.01); the percentage of adherent patients (PDC ≥ 0.8) for DPP4 inhibitors was 59.5%, while that of pioglitazone was 52.4% (p < 0.01); OR of adherence for DPP inhibitor was 1.41 (95% CI 1.25–1.59, p < 0.01) compared with that for pioglitazone; 56.7% of patients on DPP4 were persistent compared with 46.3% of patients on pioglitazone (p < 0.01)

Nishimura et al., 2019 [27]

The Japan Medical Data Center (JMDC) database and the Medical Data Vision (MDV) database

Proportion of days covered (PDC)

Percentage of patients who remained on treatment after one-year follow-up

40,908 and 90,421 (from JMDC and MDV, respectively) adult T2DM patients aged 18 or older in Japan who had been issued at least one prescription for the index medication during January 2011 to December 2015

1 year

One-year persistence rates were 67.4% and 77.2% for treatment naïve patients identified from JMDC and MDV, respectively; One-year persistence rates were 73.5% and 78.8% for previously treated patients identified from JMDC and MDV; one-year adherence was 0.87 and 0.98 for treatment naive patients identified from JMDC and MDV; one-year adherence was 0.89 and 0.98 for previously treated patients identified from JMDC and MDV respectively

Insulin

Wei et al., 2017 [63]

National pharmacy database from Walgreen Co. (Deerfield, IL)

N.A

Persistence was defined as remaining on the index medication during the 1-year follow-up period

247,102 T2DM patients aged ≥ 18 who filled ≥ 1 prescription for one of the index drugs along with ≥ 1 oral antidiabetic drug (OAD) between January 2013 and June 2013

1 year

66.8% of patients (95% confidence interval [CI] = 66.6 – 67.0) remained persistent after 1-year follow-up. The mean duration of persistence was 307.9 days (standard deviation [SD] = 85.2)

Bermeo-Cabrera et al., 2018 [64]

The diabetes clinic of a tertiary care center in Mexico City

Morisky-Green Questionnaire

N.A

200 T2DM patients on insulin treatment between March 2017 and December 2017

N.A

11% scored excellent adherence; 30.5% scored moderately good adherence; 58.5% scored poor adherence

Perez-Nieves et al., 2018 [65]

The Truven Health MarketScan® Research Databases

Proportion of days covered (PDC)

N.A

21,363 T2DM patients aged ≥ 18 who filled ≥ 1 prescription for the index drugs in 2012

3 years

33.8% of patients remained adherent (PDC after 3 years

Sambamoorthi et al., 2017 [62]

Medical, pharmacy, and laboratory claims data from Humana Medicare Advantage Prescription Drug (MAPD) plans

N.A

Persistence was defined as the absence of any 90-day gap between rapid-acting insulin prescriptions

3,927 elderly Medicare beneficiaries (65 years or older), who added therapy with rapid-acting insulin between July 2007 and December 2011

1 year

20.8% of patients remained persistent after 1-year follow-up

Hadjiyianni et al., 2017 [87]

Administrative claims database from Japan Medical Data Center

N.A

Persistence was defined as having a prescription gap of < 30 days

827 T2DM patients aged less than 70 years who were employed by middle-to-large size companies in Japan and with at least one pharmacy claim for the index drug between May 1, 2006 and April 30, 2013

1 year

36% of patients remained persistent. 42% had at least one gap of > 30-day prescription gap. 22% discontinued after the first prescription gap

Glucagon-like peptide-1 receptor agonists

Mody et al., 2021 [75]

HealthCore Integrated Research Database (HIRD)

Proportion of days covered (PDC)

The number of days of continuous treatment without a gap in therapy of greater than 45 days

18,650 T2DM patients aged 18 or older who initiated one of the index medications between February 2018 and December 2018; matched cohorts through propensity score matching, consisting of 12,919 patients on dulaglutide, 3,852 patients on semaglutide, and 1,879 on exenatide BCise

6 months

Dulaglutide users had significantly higher mean PDC (0.75 vs. 0.67, p < 0.0001) and proportion of persistent patients (69.2% vs. 59.2%, p < 0.0001) compared with semaglutide users; dulaglutide users had significantly higher mean PDC (0.75 vs. 0.63, p < 0.0001) and proportion of persistent patients (67.9% vs. 50.6%, p < 0.0001) compared with exenatide BCise users

Tofe et al., 2021 [77]

Hospital recrods at Son Espases University Hospital, Palma de Mallorca, Spain

Days covered by medication fills as measured by quarterly evaluation of pharmacy claims

Discontinuation rates registered in patients' records at each visit during the follow-up period

298 T2DM patients aged 18 or older who initiated dulaglutide or sc semaglutide between January 2019 and June 2020; matched cohorts through propensity score matching consisting of 183 patients on dulaglutide and 115 patients on sc semaglutide

6 months

84.25% of dulaglutide users were adherent at 6 months; 83.71% of sc semaglutide users were adherent at 6 months; 20.5% of dulaglutide users discontinued at 6 months; 21.4% of sc semaglutide users discontinued at 6 months

Mody et al., 2018 [71]

HealthCore Integrated Research Database (HIRD)

Proportion of days covered (PDC)

The number of days of continuous treatment without a gap in therapy of greater than 45 days

1,970 T2DM patients aged 18 or older with at least one pharmacy claim for dulaglutide between November 1, 2014 and November 30, 2015

183 days

61% of patients were adherent (PDC ≥ 0.8); the mean PDC was 0.76; 37% patients discontinued; the mean number of days of persistent use of dulaglutide was 152 days

Uzoigwe et al., 2021 [74]

The Optum Clinformatics® Data Mart

Proportion of days covered (PDC)

The number of days without a prescription gap of > 60 days

56,715 T2DM patients aged 18 or older who initiated treatment with GLP-1RA agent between January 1, 2018 and April 30, 2019 (5.8% semaglutide QW, 49.2% dulaglutide, 30.3% liraglutide, 14.7% exenatide QW)

6 months or 1 year

The proportion of persistent patients at 6 months (1 year) was 74.0% (67.0%) for semaglutide QW; 66.4% (56.0%) for dulaglutide; 54.1% (40.4%) for liraglutide; 48.6% (35.5%) for exenatide QW; the proportion of adherent (PDC ≥ 0.8) patients at 6 months (1 year) was 44.7% (39.1%) for semaglutide QW; 53.8% (43.2%) for dulaglutide; 39.9% (30.0%) for liraglutide; 38.8% (27.7%) for exenatide QW

Durden et al., 2019 [73]

IBM Watson Health Explorys Universe Dataset

Proportion of days covered (PDC)

Continuous treatment lasting at least 12 or 18 months

8329 T2DM patients aged 18 or older who initiated GLP-1RA therapy between January 1, 2010 and January 1, 2017

1.5 year

The proportion of adherent (PDC ≥ 0.8) patients who experienced improvements in HbA1c level or body weight or both within 6 months was 45.0%, 43.4%, and 46.4%, respectively, compared with 37.1%, 39.0%, and 38.6% for those who did not (p < 0.001 for all comparisons); the proportion of discontinuation patients at 18 months who experienced improvements in HbA1c level or body weight or both within 6 months was 61.4%, 61.9%, and 60.0%, respectively, compared with 67.9%, 67.5%, and 66.7% for those who did not (p < 0.001 for all comparisons)

Rapuch et al., 2021 [88]

IQVIA Real World Data Adjudicated Pharmacy Claims

N.A

Continuous treatment without switching to a different medication class or without a prescription gap of at least twice the expected duration of the previous fill

15,074 T2DM patients aged 18 or older who initiated GLP-1RA therapy between January 1, 2015 and December 31, 2016

1 year

The proportion of persistent patients at 12 months was 39% for all GLP-1 RA agents; the median number of days of persistent treatment was 220 for all GLP-1 RA agents; the proportion of persistent patients at 12 months was 51% for dulaglutide; the proportion of persistent patients at 12 months was 35% for exenatide QW; the proportion of persistent patients at 12 months was 21% for exenatide BID; the proportion of persistent patients at 12 months was 36% for liraglutide

Alatorre et al., 2017 [76]

The Truven Health MarketScan Commercial Claims and Encounters, The Medicare Supplemental and Coordination of Benefits

Proportion of days covered (PDC)

The number of days of continuous treatment without > 60 days of gap in the prescription

16,197 T2DM patients aged 18 or older with at least 1 prescription claim for a GLP-1RA agent between November 5, 2014 to April 30, 2015

6 months

Mean PDC at 6 months was 0.72, 0.61, and 0.71 for dulaglutide, exenatide QW, and liraglutide, respectively; the proportion of patients who discontinued treatment before the end of 6-month follow-up was 26.2%, 48.4%, and 35.6% for dulaglutide, exenatide QW, and liraglutide, respectively

Svensson et al., 2021 [69]

The National Diabetes Register

N.A

Continuous treatment without ≥ 60 days prescription gap

17,361 T2DM patients aged 18 or older who initiated GLP-1RA treatment between May 23, 2015 and October 15, 2017

 ≥ 75 days

Proportion of persistent patients at one-year was 72.6% for exenatide QW, 80.9% for liraglutide, 71.2% for lixisenatide, and 87.7% for dulaglutide

Carls et al., 2017 [89]

The Optum/Humedica SmartFile Database

Proportion of days covered (PDC)

Continuous treatment without ≥ 30 days prescription gap

873 T2DM patients aged 18 or older who initiated DPP4 inhibitors or GLP1RA between January 2007 and December 2014 (221 GLP1RA users)

1 year

29% of patients were adherent (PDC ≥ 0.8), while 45.2% of GLP-1RA users discontinued

Nguyen et al., 2017 [72]

The Humana administrative claims database

Proportion of days covered (PDC)

N.A

5133 T2DM patients aged between 65 and 90, who initiated treatment with exenatide QW, exenatide BID, or liraglutide QD between January 1, 2020 and February 28, 2014

6 months

The proportion of adherent patients (PDC ≥ 0.8) at 6 month was 43.2%, 35.0%, 39.0% for exenatide QW, liraglutide, exenatide BID, respectively; the mean PDC at 6 months was 0.63, 0.57, 0.61 for exenatide QW, liraglutide, exenatide BID, respectively

Thiazolidinediones

Flory et al., 2017 [7]

The OptumLabs Data Warehouse (OLDW)

Daily medication possession probability (daily MPP)

N.A

11,067 T2DM patients aged 18 or older who received a first electronic prescription for one of the index medications during the 2012 calendar year (409 pioglitazone users)

1 year

The daily MPP at one year was 0.36

McGovern et al., 2018 [1]

The Royal College of General Practitioners Research and Surveillance Centre (RCGP-RSC) database

N.A

Absence of a gap in prescriptions of greater than or equal to 90 days

60,327 T2DM patients who initiated treatment with one of the index medications between January 1, 2005 and December 31, 2015 (6,084 TZD users)

6 months, 1 year, 2 years, and 5 years

Median persistence was 1.55 years; percentages of persistent patients at 6 months, 1 year, 2 years, and 5 years were 75.6%, 61.2%, 43.0%, and 15.7%, respectively; HR of discontinuation for TZD compared with metformin was 1.71 (95% CI 1.64 to 1.77, p < 0.001)

Gor et al., 2020 [57]

The MarketScan® commercial claims and encounters database

Proportion of days covered (PDC)

The number of days before the gap of two times the days’ supply or the end of follow-up

9019 T2DM patients (aged 18 and above) with non-dialysis chronic kidney disease, who initiated either a DPP4 inhibitor or pioglitazone (2,017 pioglitazone users)

1 year

Mean PDC at one year was 0.72; the proportion of adherent (PDC ≥ 0.8) patients was 52.4%; the proportion of persistent patients at one year was 46.3%

Nishimura et al., 2019 [27]

The Japan Medical Data Center (JMDC) database and the Medical Data Vision (MDV) database

Proportion of days covered (PDC)

Percentage of patients who remained on treatment after one-year follow-up

40,908 and 90,421 (from JMDC and MDV, respectively) adult T2DM patients aged 18 or older in Japan who had been issued at least one prescription for the index medication during January 2011 to December 2015 (1,246 TZD users)

1 year

One-year persistence rates were 51.2% and 57.2% for treatment naïve patients identified from JMDC and MDV, respectively; One-year persistence rates were 50.0% and 48.1% for previously treated patients identified from JMDC and MDV; one-year adherence was 0.828 and 0.961 for treatment naive patients identified from JMDC and MDV; one-year adherence was 0.897 and 0.957 for previously treated patients identified from JMDC and MDV respectively