Remission of Type 2 Diabetes in Linked Health Records: Uncommon, Short-Lived, and More Often Ended by Treatment Restart Than by Rising HbA1c

Objective

To estimate how often remission of type 2 diabetes is recorded in routine care, how long it lasts, and what ends it, separating a return of hyperglycemia from a restart of treatment.

Research design and methods

We studied 136,781 adults aged 18 years or older with laboratory-confirmed type 2 diabetes in the Protégé linked electronic health record (EHR) and claims database. The 96,817 adults with glucose-lowering treatment recorded at or before cohort entry formed the primary (previously treated) cohort; 39,964 adults with no treatment recorded at entry were analyzed in parallel. Remission required two HbA1c values <6.5%, 90–365 days apart, the first at least 3 months after all glucose-lowering drugs were discontinued, with no therapy recorded between them. After remission we followed glycemic relapse (HbA1c ≥6.5%) and treatment restart (a new outpatient prescription or dispensed fill) separately, with death as a competing event (Aalen–Johansen).

Results

Remission was documented in 4.33% of previously treated adults cohort and 15.57% in the cohort of untreated adults at entry. Five-year cumulative incidence (Aalen–Johansen) was 3.82% (95% CI 3.69–3.93) and 13.27% (12.90–13.59) in each cohort, respectively. Remission was less common with greater baseline treatment burden: exploratory adjusted 5-year incidence was 4.65% in adults with 1 glucose-lowering class with a treatment episode recorded at or before entry, 3.62% with two, 2.69% with three, and 2.02% with four or more such drugs.. The Median Kaplan–Meier duration of first remission was 226 days (IQR 93–855) in previously treated adults and 371 days (166–1,027) in adults untreated at entry; 37.9% (treated cohort) and 23.1% (untreated cohort) of episodes had ended by 152 days. Among remission episodes that had ended, median duration was 159 days (71–362) and 265 days (129–565) for the treated and untreated at entry cohort, respectively. Within 5 years of remission in previously treated adults, the first event ending remission was glycemic relapse in 31.94%, treatment restart in 47.83%, and death in 4.65%.Treatment restart was about 1.5 times as common as glycemic relapse as the first event ending remission. A second remission followed within 5 years in 19.53% of previously treated and 24.10% of untreated remitters.

Conclusions

Recorded remission was uncommon and short-lived, and it ended more often with a treatment restart than with a rise in HbA1c. Studies of remission in real-world data should report relapse and restart separately and state how they confirm remission and establish that treatment stopped.

Article highlights

Why did we undertake this study? Most real-world studies count any end of remission as relapse, mixing rising HbA1c with treatment restart.

What is the specific question we wanted to answer? How often is remission recorded in routine care, how long does it last, and what ends it?

What did we find? About 1 in 23 previously treated adults had remission (4.33% ever recorded; 3.82% by 5 years); Remission episodes had a median duration of about 7.5 months (37.9% had ended by 5 months) and ended more often with a treatment restart than with rising HbA1c (47.83% vs 31.94% as first event by 5 years). Remission was less common with greater baseline treatment burden after exploratory adjustment (4.65% with 1 glucose-lowering class with a treatment episode recorded at or before entry, 3.62% with two, 2.69% with three, and 2.02% with four or more such drugs).

What are the implications of our findings? Remission studies and quality measures should report glycemic relapse and treatment restart separately.