Achievement of HbA1c and weight targets in adults with type 2 diabetes on once weekly injectable glucagon‐like peptide‐1 receptor agonist therapy in UK primary care: A retrospective, real‐world study

Abstract

Aims

Evaluate glycated haemoglobin (HbA1c) and weight changes after 6 months of once‐weekly (QW) injectable glucagon‐like peptide‐1 receptor agonist (GLP‐1 RA) therapy in UK primary care.

Materials and Methods

Retrospective, non‐interventional study, using the Clinical Practice Research Datalink Aurum primary care database, identified adults with type 2 diabetes (T2D) newly initiating a QW injectable GLP‐1 RA between January 2020 and November 2021. Dual primary outcomes were proportion of patients with (1) HbA1c < 7% (<53 mmol/mol) and (2) weight loss categories (from 0% to 15+%) after 6 months of continuous GLP‐1 RA therapy.

Results

The study cohort comprised 10 816 adults: mean ± standard deviation age 58.8 ± 11.4 years, baseline HbA1c 9.3% ± 1.7% (78.1 ± 18.6 mmol/mol) and body mass index 36.6 ± 7.2 kg/m². Of 5236 patients with data, 32.8% achieved HbA1c < 7% after 6 months; this proportion was higher for time since T2D diagnosis <5 years (34.1%) versus longer disease duration: ≥5–<10 years (28.0%), ≥10–<15 years (18.7%) and ≥15 years (19.3%). Of 3963 patients with weight data, 22.0% did not lose weight; 34.0%, 27.0%, 11.4% and 5.6% achieved weight reductions of >0%–<5%, ≥5%–<10%, ≥10%–<15% and ≥15%, respectively. No major differences in weight loss were observed by diabetes duration.

Conclusions

Two thirds of T2D patients receiving QW injectable GLP‐1 RA for 6 months did not attain target HbA1c < 7%, and less than half and one‐quarter of patients achieved ≥5% and ≥10% weight loss, respectively. Results suggest an unmet need for better clinical management of T2D in UK primary care.

1. INTRODUCTION

Type 2 diabetes (T2D) is associated with a significant health, social and economic burden globally due to its high incidence and the morbidity of its long‐term complications. ¹ , ² It is well established that early glycaemic control is an important intervention to reduce the risk of long‐term complications in T2D. ³ However, despite the availability of multiple classes of treatments for T2D, a substantial number of patients do not reach targets for glycaemic control or other key metabolic parameters such as weight loss. ⁴ , ⁵ This need for better glycaemic control is reinforced by data from the National Diabetes Audit, which show that almost one‐half of patients with T2D in England have HbA1c levels above 7%. ⁶ Results from international studies further confirm that only around 40%–50% of patients with T2D are currently achieving guideline‐recommended glucose targets. ⁵ , ⁷

Glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) are integral to national and international T2D treatment guidelines, and three once‐weekly (QW) injectable GLP‐1 RAs are currently available in the United Kingdom: exenatide QW (approved in January 2012), ⁸ dulaglutide (approved in January 2015) ⁹ and semaglutide subcutaneous (sc) (approved in January 2019). ¹⁰ According to National Institute for Health and Care Excellence (NICE) guidelines, GLP‐1 RAs can be considered as part of triple therapy for people with T2D when metformin and two other oral anti‐diabetes drugs are not effective, not tolerated or contraindicated. ¹¹ American Diabetes Association (ADA)/European Association for the Study of Diabetes (EASD) guidelines recommend metformin and/or agent(s), including GLP‐1 RAs, that provide adequate efficacy to achieve and maintain glycaemic treatment goals in T2D and position high‐dose dulaglutide, semaglutide and tirzepatide as very high‐efficacy approaches for achieving these glucose‐lowering goals. ³

Current NICE glycaemic targets align with those in the recent ADA/EASD 2022 consensus report, where the goal of management is to attain HbA1c < 7% (<53 mmol/mol) after 6 months. ³ , ¹¹ Weight loss targets are 5%–10% to confer metabolic improvement and 10%–15% for a disease‐modifying effect. ³ Similar glycaemic targets have been set in England by the Quality and Outcomes Framework (QOF) for the management and payment of general practitioners in the national health service, which stipulates an HbA1c < 7.5% (<58 mmol/mol) for patients with T2D in UK primary care. ¹² For patients receiving GLP‐1 RAs, NICE states that therapy should only be continued if there is a beneficial metabolic response: defined as a reduction of at least 1% (11 mmol/mol) in HbA1c and weight loss of at least 3% of initial body weight in 6 months. ¹¹

The use of GLP‐1 RAs has been shown to improve the management of hyperglycaemia in T2D and to provide the additional benefits of weight loss and improved cardiovascular risk factors. ¹³ , ¹⁴ , ¹⁵ , ¹⁶ , ¹⁷ , ¹⁸ However, available evidence suggests that a large proportion of patients with T2D currently do not meet the targets for beneficial metabolic response, as set out by NICE, QOF and the ADA/EASD, when prescribed QW GLP‐1 RAs, both in the United Kingdom and internationally, although the precise proportion remains unknown. ¹³ , ¹⁹ , ²⁰ Given the importance of early and intensive glycaemic control in T2D for preventing the development of long‐term disease‐related complications, it is useful to understand what proportion of patients on QW injectable GLP‐1 RAs are attaining the key metabolic targets and to quantify inadequate goal achievement. Therefore, this retrospective study aimed to evaluate HbA1c and weight reduction targets in patients with T2D after 6 months of any QW injectable GLP‐1 RA therapy in UK primary care clinical practice. Additionally, the association of HbA1c < 7% (<53 mmol/mol) and weight reductions with treatment, clinical and socio‐demographic factors are described. Longer term achievement of HbA1c targets and weight reductions were also assessed.

2. MATERIALS AND METHODS

2.1. Study design and setting

This retrospective, new‐user, non‐interventional cohort study used primary care data from the Clinical Practice Research Datalink (CPRD) Aurum database to identify adults with diagnosed T2D first prescribed (the index date/event) exenatide QW, dulaglutide or semaglutide sc (referred to hereafter as QW injectable GLP‐1 RAs) between 1 January 2020 and 31 November 2021, inclusive (the indexing period) (Figure 1). Attainment of HbA1c and weight reduction targets were described after 6 months of continuous QW injectable GLP‐1 RA therapy and after 12 and/or 18 months of continuous use for those with sufficient follow‐up.

FIGURE 1.

Study design schematic. *Continuous use defined as a permissible gap between index once weekly (QW) injectable glucagon‐like peptide‐1 receptor agonist (GLP‐1 RA) prescriptions of ≤90 days. HbA1c, glycated haemoglobin.

2.2. Study population

Adults with T2D, newly initiating QW injectable GLP‐1 RA therapy in primary care within the indexing period, with at least 6 months' continuous use, were included in the study. For full details of study inclusion/exclusion criteria and baseline covariates, see Table S1.

2.3. Research outcomes

The dual primary outcomes of the study were to describe the proportion of patients with (1) HbA1c < 7% (<53 mmol/mol) and (2) no weight loss or weight loss of >0%–<5%, ≥5%–<10%, ≥10%–<15% and ≥15% compared with baseline, both after 6 months of continuous QW injectable GLP‐1 RA therapy. Additional stratification was also performed by T2D duration.

Secondary outcomes were to describe baseline demographics and clinical characteristics of the study population and, after 6 months of continuous QW injectable GLP‐RA use, the proportion of patients (1) achieving both a 1% (11 mmol/mol) HbA1c reduction and no weight loss or weight loss of >0%–<5%, ≥5%–<10%, ≥10%–<15% and ≥15%, overall and stratified by clinical/treatment characteristics and socio‐demographics; and (2) achieving a composite of HbA1c < 7% and no weight loss or weight loss of >0%–<5%, ≥5%–<10%, ≥10%–<15% and ≥15%. The proportion of patients not achieving ≥1% HbA1c reduction and ≥3% weight loss but continuing with index GLP‐1 RA therapy after 6 months of continuous QW injectable GLP‐1 RA use was also described. After 6, 12 and 18 months, the proportion of patients achieving (1) HbA1c < 7% or <7.5% (<58 mmol/mol) and (2) no weight loss or weight loss of >0–<5%, ≥5%–<10%, ≥10%–<15% and ≥15% was also described, overall and stratified by baseline HbA1c and body mass index (BMI), respectively. Additional analyses for BMI were carried out within ethnic minorities to reflect NICE guidelines on GLP‐1 RA therapy, which recommend BMI adjustment for certain ethnic groups. ¹¹

2.4. Exposure and outcome assessments

Continuous use was defined as treatment gaps between subsequent prescriptions of ≤90 days. Assessment of dual primary outcomes utilized the first recorded HbA1c value after 6 months (<12), 12 months (<18) and 18 months (<24) following indexing. Percentage weight reduction was calculated as baseline weight minus first recorded weight value after 6 (<12) months from indexing divided by baseline weight. Calculations were repeated after 12 (<18) months and 18 (<24) months. Objectives were assessed in subjects with a recorded HbA1c, BMI or both; therefore, the number included in each analysis differed because of data availability for the various outcomes. However, these different subsamples remained comparable with the overall study sample in terms of baseline demographic and clinical characteristics, as shown in Table S2.

2.5. Statistical analysis

For categorical variables, frequencies and percentages were reported (including missing/unknown data). For continuous variables, mean ± standard deviation (SD) values were provided.

To evaluate the impact of the COVID‐19 pandemic, sensitivity analyses were performed for the primary objectives, extending the permissible gap between index QW GLP‐1 RA prescriptions from ≤90 to ≤180 days. Additional sensitivity analyses were also performed whereby baseline weight and/or HbA1c were restricted to the 6 months up to and including the index date only. All analyses were conducted using Stata 18 software (StataCorp, College Station, TX, USA).

2.6. Ethical considerations

This study was approved by CPRD (Protocol 23_002645). Generic ethical approval for observational research approved by CPRD was granted by a Health Research Authority Research Ethics Committee (East Midlands‐Derby, UK; REC reference number 05/MRE04/87).

3. RESULTS

Of the 59 678 adults with T2D indexed on a QW GLP‐1 RA, 10816 patients met the eligibility criteria and comprised the study cohort. Of these, 5440 (50.3%) and 2478 (22.9%) had data for at least 12 and 18 months of continued index QW injectable GLP‐1 RA treatment, respectively (Figure 2). Key reasons for patient attrition were not receiving at least one weekly GLP‐1 RA prescription within the indexing period and not receiving at least 6 months of therapy, with no changes in concomitant glucose‐lowering treatment. Full details of the number of patients included in each analysis and the follow‐up times are provided in Table S3.

FIGURE 2.

Patient attrition. CPRD, Clinical Practice Research Datalink; GP, general practitioner; GLP‐1 RA, glucagon‐like peptide‐1 receptor agonist; QW, once weekly; T2D, type 2 diabetes.

3.1. Baseline demographics and clinical characteristics

Patient demographics, clinical characteristics and treatment use at baseline are shown in Table 1. Mean ± SD age was 58.8 ± 11.4 years and 51.6% were male. Mean time since T2D diagnosis was 10.6 ± 6.7 years. Mean baseline HbA1c was 9.3% ± 1.7% (78.1 ± 18.6 mmol/mol), and 94.8% of patients had HbA1c levels ≥7%. Mean baseline BMI was 36.6 ± 7.2 kg/m², and 68.6% of patients recorded a BMI of ≥30 kg/m². Overall, the index GLP‐1 RA for 51.4% of patients was dulaglutide, 48.1% semaglutide sc and 0.5% exenatide QW. Most patients started on semaglutide sc 0.25 mg or dulaglutide 0.75 mg or 1.5 mg.

TABLE 1.

Baseline demographics and clinical characteristics.

Variables	Total cohort (n = 10 816)
Age (years) at index
N	10 816
Mean ± SD	58.8 ± 11.4
Male sex	5577 (51.6)
Ethnicity
White	4095 (37.9)
South Asian	652 (6.0)
Other Asian	157 (1.5)
Afro‐Caribbean	331 (3.1)
Other Black	10 (0.1)
Mixed a	3463 (32.0)
Other	122 (1.1)
Unknown	1986 (18.4)
Socioeconomic status
1st quintile (least deprived)	1598 (14.8)
2nd quintile	1968 (18.2)
3rd quintile	2020 (18.7)
4th quintile	2417 (22.3)
5th quintile (most deprived)	2638 (24.4)
Unknown	175 (1.6)
Years since T2D diagnosis at index
N	10 816
Mean ± SD	10.6 ± 6.7
BMI (kg/m2)
N	8745
Mean ± SD	36.6 ± 7.2
BMI (kg/m2) (grouped)
<18.5	<5
≥18.5–<25.0	NR
≥25.0–<30.0	1203 (11.1)
≥30.0–<35.0	2800 (25.9)
≥35.0–<40.0	2308 (21.3)
≥40	2307 (21.3)
Unknown	2071 (19.1)
BMI (kg/m2) (grouped, ethnic minorities b )
<27.0	206 (4.4)
≥27.0	3582 (75.6)
Unknown	947 (20.0)
HbA1c (%) level
N	10 740
Mean ± SD	9.3 ± 1.7
HbA1c (%) level (grouped)
<7.0% (<53 mmol/mol)	483 (4.5)
≥7.0% (≥53 mmol/mol) to <7.5% (<58 mmol/mol)	555 (5.1)
≥7.5% (≥58 mmol/mol) to <8.0% (<64 mmol/mol)	1175 (10.9)
≥8.0% (≥64 mmol/mol) to <9.0% (<75 mmol/mol)	2889 (26.7)
≥9.0% (≥75 mmol/mol)	5638 (52.1)
Unknown	76 (0.7)
Smoking status
Current smoker	1129 (10.4)
Former smoker	3326 (30.8)
Non‐smoker	165 (1.5)
Unknown c	6196 (57.3)
Number of comorbidities
0	2949 (27.3)
1	4275 (39.5)
2	2417 (22.3)
3	856 (7.9)
4+	319 (3)
Comorbidities
Coronary heart disease	1621 (15.0)
Congestive heart failure	530 (4.9)
Chronic kidney disease	1236 (11.4)
Dyslipidaemia	2804 (25.9)
Hypertension	6412 (59.3)
Stroke	419 (3.9)
Index GLP‐1 RA
Dulaglutide	5561 (51.4)
Semaglutide sc	5199 (48.1)
Exenatide QW	56 (0.5)
Index dulaglutide dose (grouped)
0.75 mg	2587 (46.5)
1.5 mg	2937 (52.8)
3.0 mg	3 (0.1)
4.5 mg	NR
Other	34 (0.6)
Index semaglutide sc dose (grouped)
0.25 mg	4441 (85.4)
0.5 mg	502 (9.7)
1.0 mg	114 (2.2)
Other	142 (2.7)
Index exenatide QW dose (grouped)
2.0 mg	56 (100)
Concomitant anti‐diabetic medication
Acarbose	8 (0.1)
DPP‐4 inhibitors	3896 (36.0)
Meglitinides	17 (0.2)
Metformin	9288 (85.9)
Pioglitazone	348 (3.2)
SGLT‐2 inhibitors	4481 (41.1)
Sulphonylureas	3631 (33.6)
Insulin	2186 (20.2)
Concomitant anti‐diabetic medication (grouped)
0	132 (1.2)
1	2375 (22.0)
2	4090 (37.8)
3+	4219 (39.0)

Note: Data are presented as n (%) or mean ± standard deviation.

Abbreviations: BMI, body mass index; DDP‐4, dipeptidyl peptidase‐4; GLP‐1 RA, glucagon‐like peptide‐1 receptor agonist; HbA1c, glycated haemoglobin; NR, not reported (to protect primary suppression of small cell values, i.e., <5); QW, once weekly; sc, subcutaneous; SD, standard deviation; SGLT‐2, sodium glucose cotransporter‐2; T2D, type 2 diabetes.

^a Predominantly driven by a clinical code of: British or mixed British.

^b All non‐White ethnicities were considered ethnic minorities.

^c Likely driven by limited look‐back (18 months) for ascertaining smoking status.

3.2. Primary outcomes

Of the 5236 patients with a recorded HbA1c measurement, 32.8% (n = 1719) were at target HbA1c < 7% after 6 months of continuous QW injectable GLP‐1 RA therapy (Figure 3A). When stratified by time since T2D diagnosis, the proportion of patients with HbA1c < 7% after 6 months was higher among those with a T2D diagnosis <5 years (34.1%) than among those with longer disease duration: ≥5–<10 years (28.0%), ≥10–<15 years (18.7%) and ≥15 years (19.3%). Conversely, patients with HbA1c ≥ 7% after 6 months were most likely to have a longer time since T2D diagnosis: ≥5–<10 years (26.4%), ≥10–<15 years (26.2%) and ≥15 years (30.0%) versus <5 years (17.3%).

FIGURE 3.

Proportion of patients (A) with glycated haemoglobin (HbA1c) < 7% (53 mmol/mol) and (B) achieving weight reduction of ≤0%, >0%–<5%, ≥5%–<10%, ≥10%–<15% or ≥15% after 6 months of continuous once weekly (QW) injectable glucagon‐like peptide‐1 receptor agonist (GLP‐1 RA) therapy.

Of the 3963 patients with recorded weight measurements both at baseline and during follow‐up, 22.0% (n = 872) did not achieve any weight reduction after 6 months of continuous QW injectable GLP‐1 RA use, whereas 78.0% (n = 3091) lost weight. Weight reduction of >0%–<5%, ≥5%–<10%, ≥10%–<15% and ≥15% was reported by 34.0%, 27.0%, 11.4% and 5.6% of patients, respectively (Figure 3B). When stratified by years since T2D diagnosis, the proportion of patients in each weight change category was approximately evenly distributed (19.9%–29.9% of patients in each weight change category had a T2D diagnosis <5, ≥5–<10, ≥10–<15 and ≥15 years previously).

3.3. Secondary outcomes

3.3.1. ≥1% HbA1c reduction and no weight loss or weight loss of >0%–<5%, ≥5%–<10%, ≥10%–<15% and ≥15% after 6 months

Among eligible patients (n = 3339), 37.5% (n = 1252) did not have a ≥1% HbA1c reduction at 6 months and 62.5% (n = 2087) did; of these, 11.7% (n = 390) did not lose any weight. Overall, 50.8% (n = 1697) of patients achieved both a ≥1% reduction in HbA1c and lost weight, with 20.5%, 17.8%, 8.0% and 4.5% attaining weight reduction of >0%–<5%, ≥5%–<10%, ≥10%–<15% and ≥15%, respectively (Figure 4).

FIGURE 4.

Proportion of patients achieving glycated haemoglobin (HbA1c) reduction of ≥1% (11 mol/mol) overall and by weight loss categories after 6 months of continuous once weekly (QW) injectable glucagon‐like peptide‐1 receptor agonist (GLP‐1 RA) therapy. The two bars on the left‐hand side of the graphic denote the proportion of patients with HbA1c reduction of <1% or ≥1%.

As shown in Table S4, the proportion of patients who achieved HbA1c reduction ≥1% but did not lose weight was highest among those within the fifth quintile (most deprived) of socio‐economic status (13.6%), whereas weight reduction of either >0%, ≥5% or ≥10% was highest for those within the second quintile (52.6%, 33.2% and 14.1%, respectively). Attainment of both ≥1% HbA1c reduction and ≥5%, ≥10% or ≥15% weight reduction after 6 months was highest among patients with a T2D duration of <5 years (32.8%, 13.9% and 6.1%, respectively). Additionally, the proportion of patients achieving both ≥1% HbA1c reduction and weight loss of >0%, ≥5% or ≥10% was highest in those receiving one concomitant anti‐diabetes medication (56.5%, 36.6% and 14.9%, respectively) compared with those receiving none, two, or three or more concomitant anti‐diabetes medications.

3.3.2. HbA1c < 7% and either no weight loss or weight loss of >0%–<5%, ≥5%–<10%, ≥10%–<15% and ≥15% after 6 months

Of 3348 eligible patients, 34.8% (n = 1165) achieved HbA1c < 7.0%, 4.5% had HbA1c < 7.0% and no weight loss and 8.9%, 11.4%, 6.3% and 3.7% had HbA1c < 7.0% and reported a weight reduction of >0%–<5%, ≥5%–<10%, ≥10%–<15% and ≥15%, respectively (Figure S1).

3.3.3. <1% HbA1c reduction and <3% weight loss after 6 months and continuation of GLP‐1 RA therapy

Of 3339 eligible patients, 61.0% (n = 2037) did not report ≥1% reduction in HbA1c and ≥3% reduction in weight after 6 months. Of these patients, 93.2% (n = 1898) continued with index QW GLP‐1 RA therapy (Figure S2).

3.3.4. HbA1c < 7% or <7.5% after 6, 12 and 18 months

After 6, 12 and 18 months of continuous QW injectable GLP‐1 RA therapy, respectively, 32.8%, 30.4% and 27.4% of patients had HbA1c < 7.0% (Figure S3A), and 47.1%, 42.1% and 42.3% had HbA1c < 7.5% (Figure S3B). Stratification by baseline HbA1c is shown in Figure S4.

3.3.5. No weight loss or weight loss of >0%–<5%, ≥5%–<10%, ≥10%–<15% and ≥15% after 6, 12 and 18 months

At 6 months, 78.7% of patients lost weight, with 34.2%, 27.3%, 11.6% and 5.6% reporting a weight reduction of >0%–<5%, ≥5%–<10%, ≥10%–<15% and ≥15%, respectively. Similar results were observed across each time period (Figure S5A). When stratified by baseline BMI, the proportion of patients with larger weight reductions after 6 and 12 months was higher among those with a baseline BMI of ≥30 kg/m² than among those with a baseline BMI of <30 kg/m² across each time period (Figure S5B). Similarly, when stratified by baseline BMI within ethnic minorities, the proportion of patients with weight reduction after 6 and 12 months was higher among those with a baseline BMI of ≥27 kg/m² than among those with baseline BMI < 27 kg/m² across each time period (Figure S5C).

3.4. Sensitivity analyses

Sensitivity analyses for the dual primary outcomes of HbA1c (Figure S6) and weight (Figure S7), and for all secondary outcomes (data not shown), produced similar results to the main analysis.

4. DISCUSSION

Findings from this analysis of real‐world data from UK primary care reveal that many patients with T2D do not achieve glycaemic targets after 6 months of treatment with QW injectable GLP‐1 RAs, and a substantial proportion do not reach key metabolic targets set out in NICE and ADA/EASD guidelines and the QOF. Most patients (92.1%) initiated QW injectable GLP‐1 RA therapy with the recommended doses of semaglutide sc (0.25 mg) or dulaglutide (0.75 mg or 1.5 mg). In this study, two thirds of patients did not attain an HbA1c < 7% after 6 months of QW injectable GLP‐1 RA therapy. Similarly, less than half and one‐quarter of patients achieved weight reductions of at least 5% or 10% within the 6‐month treatment period, respectively, despite high mean baseline BMI. Notably, almost two thirds of patients met NICE stopping criteria for GLP‐1 RA therapy after 6 months (i.e., not meeting both ≥1% reduction in HbA1c and ≥3% weight reduction). However, over 90% of these patients continued with their QW injectable GLP‐1 RA. Over the longer term, increasing proportions of patients did not attain target HbA1c levels at 12 and 18 months, and extended time periods of GLP‐1 RA treatment did not lead to additional weight reductions, confirming the importance of clinical assessment after 6 months to identify patients unlikely to respond to therapy. Early consideration should be given to alternative therapeutic strategies in patients not achieving glycaemic and weight targets. Taken together, these findings indicate an unmet need to optimize the clinical management of T2D and ensure more patients achieve the key metabolic targets that are essential in preventing development of chronic disease‐related complications. ³ Indeed, in common with similar real‐world studies conducted in UK primary care, ¹⁹ , ²¹ the current study identified a multimorbid T2D population with elevated BMI. Most patients had at least one obesity‐related comorbidity, with hypertension and dyslipidaemia being the most common, and mean baseline BMI was high, particularly in ethnic minority groups (Table S5).

In the current study, mean HbA1c levels were ≥9% at initiation of GLP‐1 RA. This suggests that the majority of patients in the United Kingdom are not escalated to QW injectable GLP‐1 RAs until their HbA1c levels are substantially above target, at which point glycaemic control may be harder to attain. Therapeutic inertia around the prescribing of QW injectable GLP‐1 RAs in the United Kingdom is supported by recent analysis of the GOLD primary care database, which also found patients were considerably above target at the time of QW injectable GLP‐1 RA initiation, with over half having HbA1c levels ≥9%. ²¹ A substantial proportion of these patients also did not reach optimal HbA1c targets once initiated on QW injectable GLP‐1 RA treatment. ²¹ These findings mirror those of a similar real‐world study conducted in the United States and United Kingdom, which showed that the likelihood of achieving a target HbA1c < 7% was only 25% in patients receiving any injectable GLP‐1 RA therapy with a baseline HbA1c ≥ 9%. ²⁰

Mean time since T2D diagnosis for patients in this study was 10.6 years, which represents a longer average diabetes duration than in the pivotal GLP‐1 RA clinical trials. ²² , ²³ When stratified by years since T2D diagnosis, the greatest proportion of patients in this study with target HbA1c < 7% at 6 months was observed in those initiating QW injectable GLP‐1 RA therapy within 5 years of diagnosis. Improvement in HbA1c through prompt initiation of GLP‐1 RAs has also been highlighted in previous studies, suggesting that escalation earlier in the disease process can lead to improved metabolic outcomes. ²⁴ , ²⁵ , ²⁶ This may be associated with the underlying pathophysiology of T2D and the incretin‐based mechanism of action of these therapies. Short‐term studies suggest that incretin‐based therapies act both to protect beta‐cells and to stimulate their function, affording the opportunity to interfere with disease progression if used as an early intervention in T2D. ²⁷ A higher proportion of patients in the current study also attained the composite targets of ≥1% HbA1c reduction and ≥5% or ≥10% weight loss when initiating QW injectable GLP‐1 RA therapy within 5 years of diagnosis. Conversely, lower proportion of patients attained these composite targets when receiving more than one concomitant anti‐diabetes medication, possibly attributable to their disease having progressed further and requiring more complex treatment strategies. Collectively, these findings reinforce the clinical benefits of improved glycaemic and weight control that can be achieved through earlier introduction of GLP‐1 RAs. At a practical level, this could entail clinicians escalating more promptly to GLP‐1 RAs or other guideline‐recommended efficacious therapies in people with T2D with uncontrolled HbA1c and elevated BMI. Additionally, early consideration should also be given to more efficacious alternative therapies.

The limitations of this study were typical of those encountered when adapting routine medical treatment data for research purposes and include the potential for incomplete, inaccurate or misclassified data. The potential impact of lifestyle behaviours or interventions during the study period was not captured. The study also considered QW injectable GLP‐1 RA prescriptions, which do not indicate whether patients actually took the medication. Prescribing GLP‐1 RAs in the secondary care setting was not considered, so the first dose recorded in primary care for this study may not have been the first dose of the drug the patient was prescribed in routine clinical practice. Oral and daily GLP‐1 RAs were excluded from the analysis as a conservative approach to avoid confounding caused by an additional duration of GLP‐1 RA treatment. Additionally, the study population was not stratified by dosing of individual QW injectable GLP‐RAs as the study did not intend to investigate outcomes with individual drugs. We therefore do not know what doses patients were on for individual drugs at 6, 12 or 18 months of follow‐up. The beginning of the study period incorporated the start of the COVID‐19 pandemic, and all patients were indexed peri‐pandemic to avoid any biases introduced via indexing pre‐ versus peri‐pandemic; however, the delivery of primary care services during this period was likely to have been significantly impacted, and some of the outcome variables during this period may have been self‐reported rather than assessed directly by a clinician. Patients included in the study reflect a typical UK primary care T2D population, which supports the generalizability of results. Recommendations for future research in this area include thorough assessment of the impact of recommended lifestyle interventions on T2D treatment outcomes, when implemented alongside medications.

In conclusion, findings from this study suggest an unmet need for better clinical management of T2D in UK primary care given that a high proportion of patients treated with QW injectable GLP‐1 RAs are not attaining guideline‐recommended targets for both glycaemic control and weight loss, and many are continuing therapy despite meeting recommended stopping criteria. Notwithstanding the acknowledged limitations, this study found that two thirds of patients did not reach HbA1c < 7% after 6 months of GLP‐1 RA therapy, and less than half and one‐quarter had at least 5% or 10% weight loss, respectively. Over the longer term, increasing proportions of patients did not attain target HbA1c levels at 12 and 18 months, and extended time periods of GLP‐1 RA treatment did not appear to lead to additional weight reductions, suggesting the importance of clinical assessment after 6 months to identify those unlikely to respond to therapy.

AUTHOR CONTRIBUTIONS

Kunal Gulati was involved with the conception and design of the work, and the analysis and interpretation of the data. Katrien Wijndaele was involved with the design of the work and the interpretation of the data. Joanne Webb, Lill‐Brith von Arx and Kamlesh Khunti were involved with the conception and design of the work, and the interpretation of the data. Monica Seif and Thomas Jennison were involved with the design of the work, and the acquisition and interpretation of the data. Antonia Geneidat was involved with the analysis of the data for the work. Rosie Wild was involved with the analysis and interpretation of the data for the work. Robert Wood was involved with the design of the work, and the acquisition, analysis and interpretation of the data. All authors provided critical revision of the manuscript for important intellectual content and have participated sufficiently in the work to agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All authors have given their final approval of the manuscript to be published.

FUNDING INFORMATION

This work was funded by Eli Lilly and Company.

CONFLICT OF INTEREST STATEMENT

Kamlesh Khunti has acted as a consultant and speaker for Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly and Company, Merck Sharp & Dohme, Napp, Novartis, Novo Nordisk, Roche, Sanofi‐Aventis and Servier; has acted as a consultant, speaker or received grants for investigator‐initiated studies for AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, Merck Sharp & Dohme, Novartis, Novo Nordisk and Sanofi‐Aventis; and is the UK Study Lead for Oramed Pharmaceuticals and Applied Therapeutics. Joanne Webb, Kunal Gulati, Lill‐Brith von Arx and Katrien Wijndaele are full‐time employees and stock holders of Eli Lilly and Company. Monica Seif, Thomas Jennison, Antonia Geneidat and Rosie Wild are full‐time employees of Adelphi Real‐World, which received funds from Eli Lilly and Company to conduct this research. Robert Wood was a full‐time employee of Adelphi Real‐World at the time this work was conducted and prepared for publication.

PEER REVIEW

The peer review history for this article is available at https://www.webofscience.com/api/gateway/wos/peer-review/10.1111/dom.16201.

Supporting information

Data S1. Supporting information.

Gulati K, Wijndaele K, Webb J, et al. Achievement of HbA1c and weight targets in adults with type 2 diabetes on once weekly injectable glucagon‐like peptide‐1 receptor agonist therapy in UK primary care: A retrospective, real‐world study. Diabetes Obes Metab. 2025;27(4):2086‐2095. doi: 10.1111/dom.16201

DATA AVAILABILITY STATEMENT

The data that support the findings of this study are available from the Clinical Practice Research Datalink (CPRD) Aurum primary care database. Restrictions apply to the availability of these data, which were used under license for this study. Data are available from the authors with the permission of the CPRD.