Effect of gender on treatment outcomes in type 2 diabetes mellitus
Abstract
Aim To evaluate the effect of gender on clinical outcomes in people with type 2 diabetes mellitus (T2DM) receiving antidiabetes therapy.Methods This is a pooled analysis from nine similarly designed phase 3 and 4 randomized, controlled studies evaluating insulin glargine and an active comparator (NPH insulin, insulin lispro, premixed insulin, oral antidiabetes drugs, dietary intervention) in adults with T2DM. Impact of gender on outcomes including HbA1c, fasting plasma glucose (FPG), weight-adjusted insulin dose, and hypoglycemia incidence was evaluated after 24 weeks of treatment.Results Overall, 1651 male and 1287 female individuals were included; 49.8% and 50.2% were treated with insulin glargine or comparators, respectively. Females receiving insulin glargine were less likely than males to achieve a glycemic target of HbA1c≤7.0% (53mmol/mol) (54.3% vs 60.8%, respectively, p=0.0162); there was no difference between females and males receiving comparators (52.7% vs 51.3%, respectively, p=0.4625). Females had significantly greater reductions in FPG (3.1mg/dL, p=0.0458), required significantly higher insulin doses (0.03IU/kg, p=0.0071), and had significantly higher annual rates of symptomatic (p<0.0001), glucose-confirmed (<50 and <70mg/dL) symptomatic (p=0.0005 and p<0.0001), and severe hypoglycemia (p=0.0020) than males.Conclusions Females in this analysis had smaller reductions in HbA1c and were less likely to reach glycemic goals despite higher insulin doses and more hypoglycemic events than males. Differences in gender responses to therapy should be considered when individualizing treatment for people with T2DM.
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Insulin glargine has been found to benefit males more than females; in a pooled analysis of nine randomized control trials, men who received insulin glargine were more likely to achieve the glycemic target (60.8% in males versus 54.3% in females, p = 0.0162), and the same was noted for neutral protamine Hagedorn insulin (p = 0.0262).
“For example, insulin glargine has been found to benefit males more than females. More specifically, a pooled analysis of nine randomized control trials demonstrated that men who received insulin glargine were more likely to achieve the glycemic target (HbA1c < 7% or 53 mmol/mol) in comparison to women (percentage of achievement of glycemic control: 60.8% in males versus 54.3% in females, p = 0.016”
From Sex Differences in Response to Treatment with Glucagon-like Peptide 1 Receptor Agonists: Opportunities for a Tailored Approach to Diabetes and Obesity Care (2022) · cites this paper as [77]
Sex-specific differences have been previously identified with respect to other antidiabetic agents.
“Regarding the topic of glycemic efficacy, it is important to point out that sex-specific differences have been previously identified with respect to other antidiabetic agents.”
From Sex Differences in Response to Treatment with Glucagon-like Peptide 1 Receptor Agonists: Opportunities for a Tailored Approach to Diabetes and Obesity Care (2022) · cites this paper as [77]
Men treated with insulin glargine or dapagliflozin were more likely to achieve better glycemic target compared to women.
“For example, studies in the literature showed that men treated with insulin glargine or dapagliflozin, a sodium glucose cotransporter 2 inhibitor (SGLT2-i), were more likely to achieve better glycemic target in comparison to women [82,83].”
From Adipose Tissue: A Novel Target of the Incretin Axis? A Paradigm Shift in Obesity-Linked Insulin Resistance (2024) · cites this paper as [82]
Cites
Riddle (2003) · doi:10.2337/diacare.26.11.3080 · Cited by 1,479 · see citing works
Gender differences in insulin resistance, body composition, and energy balance
Geer, E. B., & Shen, W. (2009) · Gender Medicine · doi:10.1016/j.genm.2009.02.002 · Cited by 913 · see citing works
Hypoglycaemia: the limiting factor in the glycaemic management of type I and type II diabetes.
Cryer, P. (2002) · Diabetologia · doi:10.1007/s00125-002-0822-9 · Cited by 794 · see citing works
Fear of hypoglycemia: quantification, validation, and utilization
Cox, D. J., Irvine, A., Gonder-Frederick, L., Nowacek, G., & Butterfield, J. (1987) · Diabetes Care · doi:10.2337/diacare.10.5.617 · Cited by 579 · see citing works
Wild, D., von Maltzahn, R., Brohan, E., Christensen, T., Clauson, P., & Gonder-Frederick, L. (2007) · Patient Education and Counseling · doi:10.1016/j.pec.2007.05.003 · Cited by 545 · see citing works
Insulin glargine or NPH combined with metformin in type 2 diabetes: The LANMET study
Yki-Järvinen, H., Kauppinen-Mäkelin, R., Tiikkainen, M., Vähätalo, M., Virtamo, H., Nikkilä, K., Tulokas, T., Hulme, S., Hardy, K., McNulty, S., et al. (2006) · Diabetologia · doi:10.1007/s00125-005-0132-0 · Cited by 434 · see citing works
Janka, H. U., Plewe, G., Riddle, M. C., Kliebe-Frisch, C., Schweitzer, M. A., & Yki-Järvinen, H. (2005) · Diabetes Care · doi:10.2337/diacare.28.2.254 · Cited by 414 · see citing works
Sex disparities in treatment of cardiac risk factors in patients with type 2 diabetes.
Wexler, D., Grant, R. W., Meigs, J., Nathan, D., & Cagliero, E. (2005) · Diabetes Care · doi:10.2337/diacare.28.3.514 · Cited by 374 · see citing works
Bretzel, R. G., Nuber, U., Landgraf, W., Owens, D. R., Bradley, C., & Linn, T. (2008) · The Lancet · doi:10.1016/s0140-6736(08)60485-7 · Cited by 303 · see citing works
Nuutila, P., Knuuti, M. J., Mäki, M., Laine, H., Ruotsalainen, U., Teräs, M., Haaparanta, M., Solin, O., & Yki-Järvinen, H. (1995) · Diabetes · doi:10.2337/diab.44.1.31 · Cited by 253 · see citing works
Triple Therapy in Type 2 Diabetes
Rosenstock, J., Sugimoto, D. H., Strange, P., Stewart, J. A., Soltes-Rak, E., DAILEY, G. E., & on behalf of the Insulin Glargine 4014 Study Investigators (2006) · Diabetes Care · doi:10.2337/diacare.29.03.06.dc05-0695 · Cited by 235 · see citing works
Gender Aspects of the Role of the Metabolic Syndrome as a Risk Factor for Cardiovascular Disease
Regitz‐Zagrosek, V., Lehmkuhl, E., & Mahmoodzadeh, S. (2007) · Gender Medicine · doi:10.1016/s1550-8579(07)80056-8 · Cited by 228 · see citing works
Tang, Y., Pang, S., Chan, M. F., Yeung, G. S. P., & Yeung, M. W. (2008) · Journal of Advanced Nursing · doi:10.1111/j.1365-2648.2007.04526.x · Cited by 202 · see citing works
Gerstein, H. C., Yale, J. ‐., Harris, S. B., Issa, M., Stewart, J. A., & Dempsey, E. (2006) · Diabetic Medicine · doi:10.1111/j.1464-5491.2006.01881.x · Cited by 197 · see citing works
How hypoglycaemia can affect the life of a person with diabetes
Frier, B. M. (2007) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.796 · Cited by 196 · see citing works
Barriers to regimen adherence among persons with insulin-dependent diabetes
Glasgow, R. E., McCaul, K. D., & Schafer, L. C. (1986) · Journal of Behavioral Medicine · doi:10.1007/bf00844645 · Cited by 170 · see citing works
Adherence to Preventive Medications
Walker, E. A., Molitch, M., Kramer, M. K., Kahn, S., Ma, Y., Edelstein, S., Smith, K., Johnson, M. K., Kitabchi, A., Crandall, J., et al. (2006) · Diabetes Care · doi:10.2337/dc06-0454 · Cited by 161 · see citing works
Perreault, L., Ma, Y., Dagogo-Jack, S. E., Horton, E. S., Marrero, D. G., Crandall, J. P., Barrett-Connor, E. L., & Program, F. T. D. P. (2008) · Diabetes Care · doi:10.2337/dc07-2390 · Cited by 131 · see citing works
Fear of hypoglycaemia in adults with type 1 diabetes
Anderbro, T., Amsberg, S., Adamson, U., Bolinder, J., Lins, P. ‐., Wredling, R., Moberg, E., Lisspers, J., & Johansson, U. ‐. (2010) · Diabetic Medicine · doi:10.1111/j.1464-5491.2010.03078.x · Cited by 128 · see citing works
Færch, K., Borch‐Johnsen, K., Vaag, A. A., Jørgensen, T., & Witte, D. R. (2010) · Diabetologia · doi:10.1007/s00125-010-1673-4 · Cited by 128 · see citing works
Differences in Insulin Suppression of Free Fatty Acid Levels by Gender and Glucose Tolerance Status
Laws, A., Hoen, H. M., Selby, J. V., Saad, M. F., Haffner, S. M., & Howard, B. V. (1997) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.17.1.64 · Cited by 128 · see citing works
Gender differences in healthcare utilization and medical indicators among patients with diabetes
Shalev, V., Chodick, G., Heymann, A. D., & Kokia, E. S. (2004) · Public Health · doi:10.1016/j.puhe.2004.03.004 · Cited by 117 · see citing works
Gender differences in counterregulation to hypoglycaemia
Amiel, S. A., Maran, A., Powrie, J. K., Umpleby, A. M., & Macdonald, I. A. (1993) · Diabetologia · doi:10.1007/bf00402284 · Cited by 113 · see citing works
Nilsson, P. M., Theobald, H., Journath, G., & Fritz, T. (2004) · Scandinavian Journal of Primary Health Care · doi:10.1080/02813430310003264 · Cited by 91 · see citing works
Chiu, C.-J., & Wray, L. A. (2011) · Annals of Behavioral Medicine · doi:10.1007/s12160-010-9226-0 · Cited by 84 · see citing works
Gender influences counterregulatory hormone responses to hypoglycemia
Diamond, M. P., Jones, T. W., Caprio, S., Hallarman, L., Connolly-Diamond, M., Addabbo, M., Tamborlane, W. V., & Sherwin, R. S. (1993) · Metabolism · doi:10.1016/0026-0495(93)90152-e · Cited by 78 · see citing works
Effects of insulin on the counterregulatory response to equivalent hypoglycemia in normal females
Davis, S. N., Cherrington, A. D., Goldstein, R. E., Jacobs, J. K., & Price, L. (1993) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1993.265.5.e680 · Cited by 69 · see citing works
Flanagan, D., Vaile, J., Petley, G., Phillips, D. I. W., Godsland, I., Owens, P., Moore, V., Cockington, R., & Robinson, J. (2007) · Regulatory Peptides · doi:10.1016/j.regpep.2006.11.009 · Cited by 60 · see citing works
Blicklé, J., Hâncu, N., Piletič, M., et al. (2008) · Diabetes Obesity and Metabolism · doi:10.1111/j.1463-1326.2008.00980.x · Cited by 53 · see citing works
Gender differences in the insulin‐like growth factor axis response to a glucose load
Flanagan, D., Holt, R., Owens, P., Cockington, R. J., Moore, V., Robinson, J., Godsland, I., & Phillips, D. I. W. (2006) · Acta Physiologica · doi:10.1111/j.1748-1716.2006.01581.x · Cited by 34 · see citing works
Meneghini, L., Traylor, L., & Schwartz, S. L. (2010) · Endocrine Practice · doi:10.4158/ep09281.or · Cited by 32 · see citing works
Reduced Severe Hypoglycemia with Insulin Glargine in Intensively Treated Adults with Type 1 Diabetes
Garg, S. K., Paul, J. M., Karsten, J., et al. (2004) · Diabetes Technology & Therapeutics · doi:10.1089/dia.2004.6.589 · Cited by 29 · see citing works
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Arnetz, L., Rajamand Ekberg, N., & Alvarsson, M. (2014) · Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy · doi:10.2147/dmso.s51301 · Cited by 175 · see citing works
Rentzeperi, E., Pegiou, S., Koufakis, T., Grammatiki, M., & Kotsa, K. (2022) · Journal of Personalized Medicine · doi:10.3390/jpm12030454 · Cited by 140 · see citing works
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Joung, K.-I., Jung, G.-W., Park, H.-H., Lee, H., Park, S.-H., & Shin, J.-Y. (2020) · Scientific Reports · doi:10.1038/s41598-020-74000-4 · Cited by 61 · see citing works
De Fano, M., Malara, M., Vermigli, C., & Murdolo, G. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25168650 · Cited by 17 · see citing works
Weisman, A., Brown, R., Chu, L., Aronson, R., & Perkins, B. A. (2024) · Canadian Journal of Diabetes · doi:10.1016/j.jcjd.2023.09.001 · Cited by 8 · see citing works
- Authors
- McGill, J. B., Vlajnic, A., Knutsen, P. G., Recklein, C., Rimler, M., & Fisher, S. J.
- Affiliations
- Washington University in St. Louis (US)
- Sanofi (United States) (US)
- Medpace (United States) (US)
- Venue
- Diabetes Research and Clinical Practice
- Publisher
- Elsevier BV
- Published
- 2013-12
- Volume
- 102
- Issue
- 3
- Pages
- 167-174
- ISSN
- 0168-8227 (ISSN-L)
- OpenAlex
- W2062014697
- Cited by
- 61
- References
- 32
- Citations by year
- 2026: 2 · 2025: 4 · 2024: 7 · 2023: 3 · 2022: 5 · 2021: 6 · 2020: 5 · 2019: 7 · 2018: 4 · 2017: 4 · 2016: 5 · 2015: 8 · 2014: 1
- FWCI
- 3.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Diabetes Research and Clinical Practice (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Sanofi
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Sex and Gender in Healthcare
- Keywords
- type 2 diabetes, gender differences, insulin glargine, glycemic control, HbA1c, fasting blood glucose, hypoglycemia, insulin dose, sex differences in treatment response
- MeSH terms
- Adult, Blood Glucose, Body Weight, Diabetes Mellitus, Type 2, Female, Follow-Up Studies, Glycated Hemoglobin, Humans, Hypoglycemic Agents, Insulin, Male, Middle Aged, Prospective Studies, Sex Factors, Randomized Controlled Trials as Topic, Treatment Outcome, Clinical Trials, Phase III as Topic, Clinical Trials, Phase IV as Topic
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