scholarly journals Metformin use and risk of cancer in patients with type 2 diabetes: a cohort study of primary care records using inverse probability weighting of marginal structural models

2019 ◽  
Vol 48 (2) ◽  
pp. 527-537 ◽  
Author(s):  
Ruth E Farmer ◽  
Deborah Ford ◽  
Rohini Mathur ◽  
Nish Chaturvedi ◽  
Rick Kaplan ◽  
...  

Abstract Background Previous studies provide conflicting evidence on whether metformin is protective against cancer. When studying time-varying exposure to metformin, covariates such as body mass index (BMI) and glycated haemoglobin (HbA1c) may act as both confounders and causal pathway variables, and so cannot be handled adequately by standard regression methods. Marginal structural models (MSMs) with inverse probability of treatment weights (IPTW) can correctly adjust for such confounders. Using this approach, the main objective of this study was to estimate the effect of metformin on cancer risk compared with risk in patients with T2DM taking no medication. Methods Patients with incident type 2 diabetes (T2DM) were identified in the Clinical Practice Research Datalink (CPRD), a database of electronic health records derived from primary care in the UK. Patients entered the study at diabetes diagnosis or the first point after this when they had valid HbA1c and BMI measurements, and follow-up was split into 1-month intervals. Logistic regression was used to calculate IPTW; then the effect of metformin on all cancers (including and excluding non-melanoma skin cancer) and breast, prostate, lung, colorectal and pancreatic cancers was estimated in the weighted population. Results A total of 55 629 T2DM patients were alive and cancer-free at their study entry; 2530 people had incident cancer during a median follow-up time of 2.9 years [interquartile range (IQR) 1.3–5.4 years]. Using the MSM approach, the hazard ratio (HR) for all cancers, comparing treatment with metformin with no glucose-lowering treatment, was 1.02 (0.88–1.18). Results were robust to a range of sensitivity analyses and remained consistent when estimating the treatment effect by length of exposure. We also found no evidence of a protective effect of metformin on individual cancer outcomes. Conclusions We find no evidence that metformin has a causal association with cancer risk.

2021 ◽  
pp. 193229682199872
Author(s):  
Gregg D. Simonson ◽  
Richard M. Bergenstal ◽  
Mary L. Johnson ◽  
Janet L. Davidson ◽  
Thomas W. Martens

Background: Little data exists regarding the impact of continuous glucose monitoring (CGM) in the primary care management of type 2 diabetes (T2D). We initiated a quality improvement (QI) project in a large healthcare system to determine the effect of professional CGM (pCGM) on glucose management. We evaluated both an MD and RN/Certified Diabetes Care and Education Specialist (CDCES) Care Model. Methods: Participants with T2D for >1 yr., A1C ≥7.0% to <11.0%, managed with any T2D regimen and willing to use pCGM were included. Baseline A1C was collected and participants wore a pCGM (Libre Pro) for up to 2 weeks, followed by a visit with an MD or RN/CDCES to review CGM data including Ambulatory Glucose Profile (AGP) Report. Shared-decision making was used to modify lifestyle and medications. Clinic follow-up in 3 to 6 months included an A1C and, in a subset, a repeat pCGM. Results: Sixty-eight participants average age 61.6 years, average duration of T2D 15 years, mean A1C 8.8%, were identified. Pre to post pCGM lowered A1C from 8.8% ± 1.2% to 8.2% ± 1.3% (n=68, P=0.006). The time in range (TIR) and time in hyperglycemia improved along with more hypoglycemia in the subset of 37 participants who wore a second pCGM. Glycemic improvement was due to lifestyle counseling (68% of participants) and intensification of therapy (65% of participants), rather than addition of medications. Conclusions: Using pCGM in primary care, with an MD or RN/CDCES Care Model, is effective at lowering A1C, increasing TIR and reducing time in hyperglycemia without necessarily requiring additional medications.


2021 ◽  
Vol 22 (4) ◽  
pp. 1680
Author(s):  
Mariusz Dąbrowski

In the last decade, cancer became the leading cause of death in the population under 65 in the European Union. Diabetes is also considered as a factor increasing risk of cancer incidence and mortality. Type 2 diabetes is frequently associated with being overweight and obese, which also plays a role in malignancy. Among biological mechanisms linking diabetes and obesity with cancer hyperglycemia, hyperinsulinemia, insulin resistance, increased levels of growth factors, steroid and peptide hormones, oxidative stress and increased activity of pro-inflammatory cytokines are listed. Antidiabetic medications can modulate cancer risk through directly impacting metabolism of cancer cells as well as indirectly through impact on risk factors of malignancy. Some of them are considered beneficial (metformin and thiazolidinedions—with the exception of bladder cancer); on the other hand, excess of exogenous insulin may be potentially harmful, while other medications seem to have neutral impact on cancer risk. Inhibitors of the sodium-glucose cotransporter-2 (SGLT-2) are increasingly used in the treatment of type 2 diabetes. However, their association with cancer risk is unclear. The aim of this review was to analyze the anticancer potential of this class of drugs, as well as risks of site-specific malignancies associated with their use.


2021 ◽  
Author(s):  
Kajsa Sjöholm ◽  
Lena MS Carlsson ◽  
Per-Arne Svensson ◽  
Johanna C. Andersson-Assarsson ◽  
Felipe Kristensson ◽  
...  

<b>OBJECTIVE</b> <p>Obesity and type 2 diabetes are associated with serious, adverse health effects, including cancer. Although bariatric surgery has been shown to reduce cancer risk in patients with obesity, the effect of bariatric surgery on cancer risk in patients with obesity and diabetes is less studied. We therefore examined the long-term incidence of cancer after bariatric surgery and usual care in patients with obesity and diabetes in the matched prospective Swedish Obese Subjects (SOS) study. </p> <p><b>RESEARCH DESIGN AND METHODS</b></p> <p>The SOS study examines long-term outcomes following bariatric surgery or usual care. The current analysis includes 701 patients with obesity and type 2 diabetes at baseline, 393 of which underwent bariatric surgery, and 308 who received conventional obesity treatment. Information on cancer events was obtained from the Swedish National Cancer Register. Median follow-up time was 21.3 years (interquartile range 17.6-24.8 years, maximum 30.7 years). </p> <p><b>RESULTS</b></p> <p>During follow-up, the incidence rate for first-time cancer was 9.1 per 1000-person-years (95% CI, 7.2-11.5) in patients with obesity and diabetes treated with bariatric surgery and 14.1 per 1000-person-years (95% CI, 11.2-17.7) in patients treated with usual obesity care (HRadj=0.63; 95% CI 0.44-0.89, p=0.008). Moreover, surgery was associated with reduced cancer incidence in women (HRadj=0.58; 0.38-0.90, p=0.016), although the sex-treatment interaction was non-significant (p=0.630). In addition, diabetes remission at the 10-year follow-up was associated with reduced cancer incidence (HRadj=0.40; 95% CI 0.22-0.74, p=0.003).</p> <p><b>CONCLUSIONS</b></p> <p>These results suggest that bariatric surgery prevents cancer in patients with obesity and diabetes, and that durable diabetes remission is associated with reduced cancer risk. </p>


2017 ◽  
Vol 11 (5) ◽  
pp. 437-444 ◽  
Author(s):  
J. Wilding ◽  
C. Bailey ◽  
U. Rigney ◽  
B. Blak ◽  
M. Kok ◽  
...  

2021 ◽  
Author(s):  
Emma J Hamilton ◽  
Wendy A Davis ◽  
Ranita Siru ◽  
Mendel Baba ◽  
Paul E Norman ◽  
...  

Objective:<b> </b>To determine whether, reflecting trends in other chronic complications, incident hospitalization for diabetes-related foot ulcer (DFU) has declined over recent decades in type 2 diabetes. <p>Research design and methods:<b> </b>Participants with type 2 diabetes from the community-based Fremantle Diabetes Study Phases I (FDS1; 1,296 participants, mean age 64.0 years, 48.6% males, recruited 1993-1996) and II (FDS2; 1,509 participants, mean age 65.4 years, 51.8% males, recruited 2008-2011) were followed from entry to first hospitalization for/with DFU, death or 5 years (whichever came first). Incident rate ratios (IRRs) and incident rate differences (IRDs) were calculated for FDS2 versus FDS1 overall and in 10-year age-groups. Cox proportional hazards modelling determined independent predictors of first DFU hospitalization in the combined cohort.</p> <p>Results:<b> </b>Incident DFU hospitalization (95% CI) was 1.9 (0.9-3.3) /1,000 person-years in FDS1 during 5,879 person-years of follow-up, and 4.5 (3.0-6.4) /1,000 person-years in FDS2 during 6,915 person-years of follow-up. The crude IRR (95% CI) was 2.40 (1.17-5.28), <i>P</i>=0.013) and IRD 2.6 (0.7-4.5) /1,000 person-years (<i>P</i>=0.010). The highest incidence rate (IR) for any age-group was 23.6/1,000 person-years in FDS2 participants aged 31-40 years. Age at diabetes diagnosis (inverse), HbA<sub>1c</sub>, insulin use, height, ln(urinary albumin:creatinine), absence of any foot pulse, previous peripheral revascularization and peripheral sensory neuropathy (PSN) were independent predictors of incident hospitalization for/with DFU.</p> <p>Conclusions:<b> </b>Incident DFU hospitalizations complicating type 2 diabetes increased between FDS Phases, especially in younger participants, and were more likely in those with PSN, peripheral arterial disease and suboptimal glycemic control at baseline.</p>


2018 ◽  
Vol 7 (12) ◽  
pp. 1415-1423 ◽  
Author(s):  
Yuan Fang ◽  
Xuehong Zhang ◽  
Huilin Xu ◽  
Stephanie A Smith-Warner ◽  
Dongli Xu ◽  
...  

The excess risk of cancer observed in patients with type 2 diabetes (T2DM) may have been influenced by detection bias. The aim of this study was to examine the real association by evaluating time-varying site-specific cancer risks in newly diagnosed T2DM patients. A total of 51,324 registered cancer-free individuals newly diagnosed with T2DM between 2004 and 2014 were linked with the Shanghai Cancer Registry and the Vital Statistics through September 2015. A total of 2920 primary, invasive cancer cases were identified during 325,354 person-years period. Within 1 year following diabetes onset, participants with T2DM had higher risks of total, lung and rectal cancer in men and total, liver, pancreas, thyroid, breast and uteri cancer in women. Thereafter the incidence for overall cancer decreased and then increased along with follow-up time, with the upward trend varying by cancer, suggesting potential detection bias. After the initial 1-year period, standardized incidence ratios (SIR) and 95% CIs for overall cancer were 0.80 (95% CI 0.76–0.85) in men and 0.93 (95% CI 0.88–0.99) in women, but a higher risk of breast and thyroid cancers were observed in women, with SIR and 95% CI being 1.13 (1.01, 1.28) and 1.37 (1.11, 1.63), respectively. Our results suggest that T2DM patients are at higher risk of certain cancers; this risk particularly increases shortly after diabetes diagnosis, which is likely to be due to detection bias caused by increased ascertainment. Prevention of female breast and thyroid cancers should be paid attention in Chinese individuals with T2DM.


2021 ◽  
Author(s):  
Kajsa Sjöholm ◽  
Lena MS Carlsson ◽  
Per-Arne Svensson ◽  
Johanna C. Andersson-Assarsson ◽  
Felipe Kristensson ◽  
...  

<b>OBJECTIVE</b> <p>Obesity and type 2 diabetes are associated with serious, adverse health effects, including cancer. Although bariatric surgery has been shown to reduce cancer risk in patients with obesity, the effect of bariatric surgery on cancer risk in patients with obesity and diabetes is less studied. We therefore examined the long-term incidence of cancer after bariatric surgery and usual care in patients with obesity and diabetes in the matched prospective Swedish Obese Subjects (SOS) study. </p> <p><b>RESEARCH DESIGN AND METHODS</b></p> <p>The SOS study examines long-term outcomes following bariatric surgery or usual care. The current analysis includes 701 patients with obesity and type 2 diabetes at baseline, 393 of which underwent bariatric surgery, and 308 who received conventional obesity treatment. Information on cancer events was obtained from the Swedish National Cancer Register. Median follow-up time was 21.3 years (interquartile range 17.6-24.8 years, maximum 30.7 years). </p> <p><b>RESULTS</b></p> <p>During follow-up, the incidence rate for first-time cancer was 9.1 per 1000-person-years (95% CI, 7.2-11.5) in patients with obesity and diabetes treated with bariatric surgery and 14.1 per 1000-person-years (95% CI, 11.2-17.7) in patients treated with usual obesity care (HRadj=0.63; 95% CI 0.44-0.89, p=0.008). Moreover, surgery was associated with reduced cancer incidence in women (HRadj=0.58; 0.38-0.90, p=0.016), although the sex-treatment interaction was non-significant (p=0.630). In addition, diabetes remission at the 10-year follow-up was associated with reduced cancer incidence (HRadj=0.40; 95% CI 0.22-0.74, p=0.003).</p> <p><b>CONCLUSIONS</b></p> <p>These results suggest that bariatric surgery prevents cancer in patients with obesity and diabetes, and that durable diabetes remission is associated with reduced cancer risk. </p>


Author(s):  
Yang Hu ◽  
Xuehong Zhang ◽  
Yanan Ma ◽  
Chen Yuan ◽  
Molin Wang ◽  
...  

Abstract Background The influence of type 2 diabetes mellitus (T2D) duration on cancer incidence remains poorly understood. Methods We prospectively followed for cancer incidence 113 429 women in the Nurses’ Health Study (1978-2014) and 45 604 men in the Health Professionals Follow-up Study (1988-2014) who were free of diabetes and cancer at baseline. Cancer incidences were ascertained by review of medical records. Results In the multivariable-adjusted model incident, T2D was associated with higher risk of cancers in the colorectum, lung, pancreas, esophagus, liver, thyroid, breast, and endometrium. The pooled hazard ratios (HRs) ranged from 1.21 (95% confidence interval [CI] = 1.06 to 1.38) for colorectal cancer to 3.39 (95% CI = 2.24 to 5.12) for liver cancer. For both composite cancer outcomes and individual cancers, the elevated risks did not further increase after 8 years of T2D duration. The hazard ratio for total cancer was 1.28 (95% CI = 1.17 to 1.40) for T2D duration of 4.1-6.0 years, 1.37 (95% CI = 1.25 to 1.50) for 6.1-8.0 years, 1.21 (95% CI = 1.09 to 1.35) for 8.1-10.0 years, and 1.04 (95% CI = 0.95 to 1.14) after 15.0 years. In a cross-sectional analysis, a higher level of plasma C-peptide was found among participants with prevalent T2D of up to 8 years than those without T2D, whereas a higher level of HbA1c was found for those with prevalent T2D of up to 15 years. Conclusions Incident T2D was associated with higher cancer risk, which peaked at approximately 8 years after diabetes diagnosis. Similar duration-dependent pattern was observed for plasma C-peptide. Our findings support a role of hyperinsulinemia in cancer development.


2015 ◽  
Vol 12 (11) ◽  
pp. 1492-1499 ◽  
Author(s):  
Steven T. Johnson ◽  
Clark Mundt ◽  
Weiyu Qiu ◽  
Allison Soprovich ◽  
Lisa Wozniak ◽  
...  

Objective:To determine the effectiveness of an exercise specialist led lifestyle program for adults with type 2 diabetes in primary care.Methods:Eligible participants from 4 primary care networks in Alberta, Canada were assigned to either a lifestyle program or a control group. The program targeted increased daily walking through individualized daily pedometer step goals for the first 3 months and brisk walking speed, along with substitution of low-relative to high-glycemic index foods over the next 3 months. The outcomes were daily steps, diet, and clinical markers, and were compared using random effects models.Results:198 participants were enrolled (102 in the intervention and 96 in the control). For all participants, (51% were women), mean age 59.5 (SD 8.3) years, A1c 6.8% (SD 1.1), BMI 33.6 kg/m2 (SD 6.5), systolic BP 125.6 mmHg (SD 16.2), glycemic index 51.7 (4.6), daily steps 5879 (SD 3130). Daily steps increased for the intervention compared with the control at 3-months (1292 [SD 2698] vs. 418 [SD 2458] and 6-months (1481 [SD 2631] vs. 336 [SD 2712]; adjusted P = .002). No significant differences were observed for diet or clinical outcomes.Conclusions:A 6-month lifestyle program delivered in primary care by an exercise specialist can be effective for increasing daily walking among adults with recently diagnosed type 2 diabetes. This short-term increase in daily steps requires longer follow-up to estimate the potential impact on health outcomes.


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