Publications by category
Journal articles
Dennis J, Henley W, Weedon M, Lonergan M, Rodgers L, Jones A, Hamilton W, Sattar N, Janmohamed S, Holman R, et al (In Press). Sex and BMI alter the benefits and risks of sulfonylureas and thiazolidinediones in type 2 diabetes: a framework for evaluating stratification using routine clinical and individual trial data. Diabetes Care
McGovern A, Shields B, Hattersley A, Pearson E, Jones AG (In Press). What to do with diabetes therapies when HbA1c lowering is inadequate: add, switch, or continue? a MASTERMIND study. BMC Medicine
Shields BM, Angwin CD, Shepherd MH, Britten N, Jones AG, Sattar N, Holman R, Pearson ER, Hattersley AT (2022). Patient preference for second- and third-line therapies in type 2 diabetes: a prespecified secondary endpoint of the TriMaster study. Nature Medicine, 29(2), 384-391.
Shields BM, Dennis JM, Angwin CD, Warren F, Henley WE, Farmer AJ, Sattar N, Holman RR, Jones AG, Pearson ER, et al (2022). Patient stratification for determining optimal second-line and third-line therapy for type 2 diabetes: the TriMaster study. Nature Medicine, 29(2), 376-383.
McGovern AP, Hogg M, Shields BM, Sattar NA, Holman RR, Pearson ER, Hattersley AT, Jones AG, Dennis JM (2020). Risk factors for genital infections in people initiating SGLT2 inhibitors and their impact on discontinuation.
BMJ Open Diabetes Research & Care,
8(1), e001238-e001238.
Abstract:
Risk factors for genital infections in people initiating SGLT2 inhibitors and their impact on discontinuation
IntroductionTo identify risk factors, absolute risk, and impact on treatment discontinuation of genital infections with sodium-glucose co-transporter-2 inhibitors (SGLT2i).Research design and methodsWe assessed the relationship between baseline characteristics and genital infection in 21 004 people with type 2 diabetes initiating SGLT2i and 55 471 controls initiating dipeptidyl peptidase-4 inhibitors (DPP4i) in a UK primary care database. We assessed absolute risk of infection in those with key risk factors and the association between early genital infection and treatment discontinuation.ResultsGenital infection was substantially more common in those treated with SGLT2i (8.1% within 1 year) than DPP4i (1.8%). Key predictors of infection with SGLT2i were female sex (HR 3.64; 95% CI 3.23 to 4.11) and history of genital infection; <1 year before initiation (HR 4.38; 3.73 to 5.13), 1–5 years (HR 3.04; 2.64 to 3.51), and >5 years (HR 1.79; 1.55 to 2.07). Baseline HbA1c was not associated with infection risk for SGLT2i, in contrast to DPP4i where risk increased with higher HbA1c. One-year absolute risk of genital infection with SGLT2i was highest for those with a history of prior infection (females 23.7%, males 12.1%), compared with those without (females 10.8%, males 2.7%). Early genital infection was associated with a similar discontinuation risk for SGLT2i (HR 1.48; 1.21–1.80) and DPP4i (HR 1.58; 1.21–2.07).ConclusionsFemale sex and history of prior infection are simple features that can identify subgroups at greatly increased risk of genital infections with SGLT2i therapy. These data can be used to risk-stratify patients. High HbA1c is not a risk factor for genital infections with SGLT2i.
Abstract.
Sattar N, Holman RR, Pearson E, Shields B, Angwin C, Jenkinson C, Jones A, Jennison C, Henley W, Farmer A, et al (2020). TriMaster: randomised double-blind crossover study of a DPP4 inhibitor, SGLT2 inhibitor and thiazolidinedione as second-line or third-line therapy in patients with type 2 diabetes who have suboptimal glycaemic control on metformin treatment with or without a sulfonylurea—a MASTERMIND study protocol.
BMJ Open,
10(12), e042784-e042784.
Abstract:
TriMaster: randomised double-blind crossover study of a DPP4 inhibitor, SGLT2 inhibitor and thiazolidinedione as second-line or third-line therapy in patients with type 2 diabetes who have suboptimal glycaemic control on metformin treatment with or without a sulfonylurea—a MASTERMIND study protocol
IntroductionPharmaceutical treatment options for patients with type 2 diabetes mellitus (T2DM) have increased to include multiple classes of oral glucose-lowering agents but without accompanying guidance on which of these may most benefit individual patients. Clinicians lack information for treatment intensification after first-line metformin therapy. Stratifying patients by simple clinical characteristics may improve care by targeting treatment options to those in whom they are most effective. This academically designed and run three-way crossover trial aims to test a stratification approach using three standard oral glucose-lowering agents.Methods and analysisTriMaster is a randomised, double-blind, crossover trial taking place at up to 25 clinical sites across England, Scotland and Wales. 520 patients with T2DM treated with either metformin alone, or metformin and a sulfonylurea who have glycated haemoglobin (HbA1c) >58 mmol/mol will be randomised to receive 16 weeks each of a dipeptidyl peptidase‐4 inhibitor, sodium-glucose co-transporter-2 inhibitor and thiazolidinedione in random order. Participants will be assessed at the end of each treatment period, providing clinical and biochemical data, and their experience of side effects. Participant preference will be assessed on completion of all three treatments. The primary endpoint is HbA1c after 4 months of therapy (allowing a range of 12–18 weeks for analysis). Secondary endpoints include participant-reported preference between the three treatments, tolerability and prevalence of side effects.Ethical approvalThis study was approved by National Health Service Health Research Authority Research Ethics Committee South Central—Oxford A, study 16/SC/0147. Written informed consent will be obtained from all participants. Results will be submitted to a peer-reviewed journal and presented at relevant scientific meetings. A lay summary of results will be made available to all participants.Trial registration numbers12039221; 2015-002790-38 and NCT02653209.
Abstract.
Angwin C, Pearson E, Hattersley A (2016). Crossover studies can help the individualisation of care in type 2 diabetes: the MASTERMIND approach. Practical Diabetes, 33(4), 115-117.
Conferences
Shields B, Angwin C, Jones AG, Holman RR, Sattar N, Britten N, Pearson E, Shepherd M, Hattersley AT (2022). Let the patient choose! Patient preferences for type 2 diabetes therapy in the trimaster double-blind three-way randomised crossover trial.
Author URL.
Angwin CD, Shields BM, Jones AG, Pearson ER, Hattersley AT (2022). Raised levels of brain natriuretic peptide (BNP) in patients with type 2 diabetes but no known heart failure are rare and not associated with improved response to SGLT2 inhibitors: Findings from the TriMaster study.
Author URL.
Rickards NF, Angwin C, Pearson ER, Hattersley AT, Consortium M (2019). Patients choose glucose lowering Type 2 diabetes therapy based on their own tolerability experience rather than glycaemia or weight considerations: Evidence from the blinded TriMaster study.
Author URL.
Grubb AL, Patel K, Oram RA, Hill AV, Angwin C, McDonald TJ, Weedon MN, Hattersley AT, Owen KR, Shields BM, et al (2018). Development and validation of a clinical prediction model to identify adult patients (aged 18-50) with type 1 diabetes requiring early insulin therapy.
Author URL.
Shakweh EY, Shields BM, Angwin CD, Rodgers LR, McDonald TJ, Pearson ER, Hattersley AT, Jones AG, Consortium M (2018). Precision medicine in Type 2 diabetes: is variation in response to sitagliptin and gliclazide therapy related to drug levels?.
Author URL.
Grubb AL, Patel KA, Oram RA, Hill AV, Angwin C, McDonald TJ, Weedon MN, Hattersley AT, Shields BV, Jones AG, et al (2017). Development of a risk calculator to identify patients with Type 1 diabetes who will require early insulin therapy.
Author URL.
Jones AG, Angwin C, Hammersley S, Rogers L, Shields BM, Pearson ER, Hattersley AT (2016). The DPPIV inhibitor sitagliptin lowers postprandial glucose without improving postprandial insulin secretion: a MASTERMIND study.
Author URL.
Dennis JM, Hattersley AT, Weedon M, Angwin C, Rodgers L, Pearson ER, Henley WE, Shields BM (2015). Development of oedema is associated with an improved glycaemic response in patients initiating thiazolidinediones: a MASTERMIND study.
Author URL.
Dennis JM, Hattersley AT, Weedon M, Angwin CD, Rodgers L, Pearson ER, Henley WE, Shields BM (2015). Patients who develop oedema on initiating thiazolidinedione therapy have an improved glycaemic response: a MASTERMIND study.
Author URL.
Rodgers LR, Pearson ER, Hammersley S, Angwin CD, JMcDonald T, Shields BM, Hattersley AT, Jones AG, Consortium MASTERMIND (2015). Patients with a high fasting glucose respond better to sulphonylureas than dipeptidyl peptidase IV (DPP-IV) inhibitors: a MASTERMIND study.
Author URL.
Rodgers LR, Pearson ER, Angwin CD, Hammersley S, McDonald TJ, Shields BM, Hattersley AT, Jones AG, Consortium M (2015). Response to glucose lowering therapy can be assessed by a brief period of treatment withdrawal: a MASTERMIND study.
Author URL.
Publications by year
In Press
Dennis J, Henley W, Weedon M, Lonergan M, Rodgers L, Jones A, Hamilton W, Sattar N, Janmohamed S, Holman R, et al (In Press). Sex and BMI alter the benefits and risks of sulfonylureas and thiazolidinediones in type 2 diabetes: a framework for evaluating stratification using routine clinical and individual trial data. Diabetes Care
Hattersley A, Shields B, Dennis J, Angwin C, Warren F, Henley W, Farmer A, Sattar N, Holman R, Jones A, et al (In Press). TriMaster: randomised double-blind crossover trial of a DPP4-inhibitor, SGLT2-inhibitor and thiazolidinedione to evaluate differential glycaemic response to therapy based on obesity and renal function.
Abstract:
TriMaster: randomised double-blind crossover trial of a DPP4-inhibitor, SGLT2-inhibitor and thiazolidinedione to evaluate differential glycaemic response to therapy based on obesity and renal function
Abstract
. Precision medicine aims to target treatment to an individual based on their clinical features. A differential drug response, critical to using these features for therapy selection, has never been examined directly in type 2 diabetes. We tested two specific hypotheses: 1) individuals with BMI > 30kg/m2, compared with BMI ≤ 30kg/m2, have greater glucose lowering with thiazolidinediones than DPP4-inhibitors, and 2) individuals with eGFR 60-90mls/min/1.73m2 compared with eGFR > 90mls/min/1.73m2 have greater glucose lowering with DPP4-inhibitors than SGLT2-inhibitors. The primary endpoint for both hypotheses was the achieved HbA1c difference between strata for the two drugs. We conducted a UK based randomised, double-blind, three-way crossover trial of 16 weeks treatment with each of sitagliptin 100mg/day, canagliflozin 100mg/day and pioglitazone 30mg/day added to metformin alone or metformin plus sulfonylurea. Overall, the achieved HbA1c was similar for the three drugs. Participants with BMI > 30kg/m2, compared with BMI ≤ 30kg/m2, had a 2.88 mmol/mol (95% CI 0.98,4.79) lower HbA1c on pioglitazone than on sitagliptin (n = 356, P = 0.003). Participants with eGFR 60-90mls/min/1.73m2, compared with eGFR > 90mls/min/1.73m2, had a 2.90 mmol/mol (95% CI 1.19,4.61) lower HbA1c on sitagliptin than on canagliflozin (n = 342, P = 0.001). In this first precision medicine trial in type 2 diabetes, our findings support the use of simple routinely available measures to identify the drug likely to deliver the greatest glycaemic reduction.
Abstract.
McGovern A, Shields B, Hattersley A, Pearson E, Jones AG (In Press). What to do with diabetes therapies when HbA1c lowering is inadequate: add, switch, or continue? a MASTERMIND study. BMC Medicine
2022
Shields B, Angwin C, Jones AG, Holman RR, Sattar N, Britten N, Pearson E, Shepherd M, Hattersley AT (2022). Let the patient choose! Patient preferences for type 2 diabetes therapy in the trimaster double-blind three-way randomised crossover trial.
Author URL.
Shields BM, Angwin CD, Shepherd MH, Britten N, Jones AG, Sattar N, Holman R, Pearson ER, Hattersley AT (2022). Patient preference for second- and third-line therapies in type 2 diabetes: a prespecified secondary endpoint of the TriMaster study. Nature Medicine, 29(2), 384-391.
Shields BM, Dennis JM, Angwin CD, Warren F, Henley WE, Farmer AJ, Sattar N, Holman RR, Jones AG, Pearson ER, et al (2022). Patient stratification for determining optimal second-line and third-line therapy for type 2 diabetes: the TriMaster study. Nature Medicine, 29(2), 376-383.
Angwin CD, Shields BM, Jones AG, Pearson ER, Hattersley AT (2022). Raised levels of brain natriuretic peptide (BNP) in patients with type 2 diabetes but no known heart failure are rare and not associated with improved response to SGLT2 inhibitors: Findings from the TriMaster study.
Author URL.
2020
McGovern AP, Hogg M, Shields BM, Sattar NA, Holman RR, Pearson ER, Hattersley AT, Jones AG, Dennis JM (2020). Risk factors for genital infections in people initiating SGLT2 inhibitors and their impact on discontinuation.
BMJ Open Diabetes Research & Care,
8(1), e001238-e001238.
Abstract:
Risk factors for genital infections in people initiating SGLT2 inhibitors and their impact on discontinuation
IntroductionTo identify risk factors, absolute risk, and impact on treatment discontinuation of genital infections with sodium-glucose co-transporter-2 inhibitors (SGLT2i).Research design and methodsWe assessed the relationship between baseline characteristics and genital infection in 21 004 people with type 2 diabetes initiating SGLT2i and 55 471 controls initiating dipeptidyl peptidase-4 inhibitors (DPP4i) in a UK primary care database. We assessed absolute risk of infection in those with key risk factors and the association between early genital infection and treatment discontinuation.ResultsGenital infection was substantially more common in those treated with SGLT2i (8.1% within 1 year) than DPP4i (1.8%). Key predictors of infection with SGLT2i were female sex (HR 3.64; 95% CI 3.23 to 4.11) and history of genital infection; <1 year before initiation (HR 4.38; 3.73 to 5.13), 1–5 years (HR 3.04; 2.64 to 3.51), and >5 years (HR 1.79; 1.55 to 2.07). Baseline HbA1c was not associated with infection risk for SGLT2i, in contrast to DPP4i where risk increased with higher HbA1c. One-year absolute risk of genital infection with SGLT2i was highest for those with a history of prior infection (females 23.7%, males 12.1%), compared with those without (females 10.8%, males 2.7%). Early genital infection was associated with a similar discontinuation risk for SGLT2i (HR 1.48; 1.21–1.80) and DPP4i (HR 1.58; 1.21–2.07).ConclusionsFemale sex and history of prior infection are simple features that can identify subgroups at greatly increased risk of genital infections with SGLT2i therapy. These data can be used to risk-stratify patients. High HbA1c is not a risk factor for genital infections with SGLT2i.
Abstract.
Sattar N, Holman RR, Pearson E, Shields B, Angwin C, Jenkinson C, Jones A, Jennison C, Henley W, Farmer A, et al (2020). TriMaster: randomised double-blind crossover study of a DPP4 inhibitor, SGLT2 inhibitor and thiazolidinedione as second-line or third-line therapy in patients with type 2 diabetes who have suboptimal glycaemic control on metformin treatment with or without a sulfonylurea—a MASTERMIND study protocol.
BMJ Open,
10(12), e042784-e042784.
Abstract:
TriMaster: randomised double-blind crossover study of a DPP4 inhibitor, SGLT2 inhibitor and thiazolidinedione as second-line or third-line therapy in patients with type 2 diabetes who have suboptimal glycaemic control on metformin treatment with or without a sulfonylurea—a MASTERMIND study protocol
IntroductionPharmaceutical treatment options for patients with type 2 diabetes mellitus (T2DM) have increased to include multiple classes of oral glucose-lowering agents but without accompanying guidance on which of these may most benefit individual patients. Clinicians lack information for treatment intensification after first-line metformin therapy. Stratifying patients by simple clinical characteristics may improve care by targeting treatment options to those in whom they are most effective. This academically designed and run three-way crossover trial aims to test a stratification approach using three standard oral glucose-lowering agents.Methods and analysisTriMaster is a randomised, double-blind, crossover trial taking place at up to 25 clinical sites across England, Scotland and Wales. 520 patients with T2DM treated with either metformin alone, or metformin and a sulfonylurea who have glycated haemoglobin (HbA1c) >58 mmol/mol will be randomised to receive 16 weeks each of a dipeptidyl peptidase‐4 inhibitor, sodium-glucose co-transporter-2 inhibitor and thiazolidinedione in random order. Participants will be assessed at the end of each treatment period, providing clinical and biochemical data, and their experience of side effects. Participant preference will be assessed on completion of all three treatments. The primary endpoint is HbA1c after 4 months of therapy (allowing a range of 12–18 weeks for analysis). Secondary endpoints include participant-reported preference between the three treatments, tolerability and prevalence of side effects.Ethical approvalThis study was approved by National Health Service Health Research Authority Research Ethics Committee South Central—Oxford A, study 16/SC/0147. Written informed consent will be obtained from all participants. Results will be submitted to a peer-reviewed journal and presented at relevant scientific meetings. A lay summary of results will be made available to all participants.Trial registration numbers12039221; 2015-002790-38 and NCT02653209.
Abstract.
2019
Rickards NF, Angwin C, Pearson ER, Hattersley AT, Consortium M (2019). Patients choose glucose lowering Type 2 diabetes therapy based on their own tolerability experience rather than glycaemia or weight considerations: Evidence from the blinded TriMaster study.
Author URL.
2018
Grubb AL, Patel K, Oram RA, Hill AV, Angwin C, McDonald TJ, Weedon MN, Hattersley AT, Owen KR, Shields BM, et al (2018). Development and validation of a clinical prediction model to identify adult patients (aged 18-50) with type 1 diabetes requiring early insulin therapy.
Author URL.
Shakweh EY, Shields BM, Angwin CD, Rodgers LR, McDonald TJ, Pearson ER, Hattersley AT, Jones AG, Consortium M (2018). Precision medicine in Type 2 diabetes: is variation in response to sitagliptin and gliclazide therapy related to drug levels?.
Author URL.
2017
Grubb AL, Patel KA, Oram RA, Hill AV, Angwin C, McDonald TJ, Weedon MN, Hattersley AT, Shields BV, Jones AG, et al (2017). Development of a risk calculator to identify patients with Type 1 diabetes who will require early insulin therapy.
Author URL.
2016
Angwin C, Pearson E, Hattersley A (2016). Crossover studies can help the individualisation of care in type 2 diabetes: the MASTERMIND approach. Practical Diabetes, 33(4), 115-117.
Jones AG, Angwin C, Hammersley S, Rogers L, Shields BM, Pearson ER, Hattersley AT (2016). The DPPIV inhibitor sitagliptin lowers postprandial glucose without improving postprandial insulin secretion: a MASTERMIND study.
Author URL.
2015
Dennis JM, Hattersley AT, Weedon M, Angwin C, Rodgers L, Pearson ER, Henley WE, Shields BM (2015). Development of oedema is associated with an improved glycaemic response in patients initiating thiazolidinediones: a MASTERMIND study.
Author URL.
Dennis JM, Hattersley AT, Weedon M, Angwin CD, Rodgers L, Pearson ER, Henley WE, Shields BM (2015). Patients who develop oedema on initiating thiazolidinedione therapy have an improved glycaemic response: a MASTERMIND study.
Author URL.
Rodgers LR, Pearson ER, Hammersley S, Angwin CD, JMcDonald T, Shields BM, Hattersley AT, Jones AG, Consortium MASTERMIND (2015). Patients with a high fasting glucose respond better to sulphonylureas than dipeptidyl peptidase IV (DPP-IV) inhibitors: a MASTERMIND study.
Author URL.
Rodgers LR, Pearson ER, Angwin CD, Hammersley S, McDonald TJ, Shields BM, Hattersley AT, Jones AG, Consortium M (2015). Response to glucose lowering therapy can be assessed by a brief period of treatment withdrawal: a MASTERMIND study.
Author URL.