INTRODUCTION

Pharmacological management of diabetes in older adults is complex and challenging. Treatment strategies for glycemic control in this population should not focus solely on blood glucose levels but must also consider a wide range of clinical factors, including the risk of hypoglycemia, physical activity levels, cognitive function, vision, nutritional status, and the presence of comorbidities. Therefore, an individualized approach tailored to the unique characteristics and circumstances of each patient is essential [1].

SPECIAL CONSIDERATIONS FOR PHARMACOLOGICAL MANAGEMENT IN OLDER PATIENTS WITH DIABETES MELLITUS

The pharmacological management of diabetes mellitus in older adults shares similarities with that of younger individuals but requires careful consideration of several key factors. These include the risk of hypoglycemia, life expectancy, the presence of comorbidities, and the degree of frailty or general weakness.

It is also crucial to assess the patient’s ability to actively participate in their treatment plan, including the feasibility of insulin or other injectable therapies and their capacity for self-monitoring of blood glucose. Cognitive impairment and depression, which are more common in older adults with diabetes [2], must be identified and addressed, as these conditions can significantly affect the treatment process and adherence. Additionally, age-related declines in kidney and liver function must be considered, as they may alter the metabolism and excretion of medications [3].

According to the Korea Diabetes Association, it is essential to evaluate specific geriatric issues, such as cognitive and emotional disorders, physical disabilities (e.g., vision or hearing impairments, malnutrition, sarcopenia, urinary incontinence, and gait disturbances), polypharmacy, and other geriatric syndromes. These factors should be integrated into the treatment plan to ensure a personalized approach [1].

Setting individualized glycemic targets is critical, considering the patient's overall health status and specific needs. Medication regimens should prioritize simplicity and safety, often starting with monotherapy, with gradual dose adjustments to minimize side effects and optimize efficacy. Once treatment is initiated, close monitoring for adverse effects and potential drug interactions is essential to ensure safety and effectiveness.

HYPOGLYCEMIA

A primary objective in managing diabetes mellitus in older adults is to achieve glycemic control without inducing hypoglycemia, thereby improving or maintaining their quality of life. Hypoglycemia is more prevalent in older adults, with slower recovery times due to diminished physiological defenses, polypharmacy, and comorbidities such as kidney dysfunction [4]. Prolonged medication half-lives resulting from reduced liver metabolism and impaired kidney function further exacerbate the risk of hypoglycemia by delaying drug clearance.

Older adults frequently experience hypoglycemia unawareness, characterized by the absence of typical hypoglycemic symptoms [4]. This lack of awareness may prevent timely intervention during the early stages of hypoglycemia, increasing the likelihood of severe episodes [5]. The risk of hypoglycemia is highest with insulin therapy and is also significant with sulfonylureas and meglitinides. In contrast, medications such as metformin, thiazolidinediones (TZDs), incretins, and sodium-glucose cotransporter 2 (SGLT2) inhibitors are associated with a lower risk of hypoglycemia.

Severe hypoglycemia is linked to increased rates of cardiovascular events and mortality [6]. A large-scale randomized controlled study identified severe hypoglycemia as a predictor of cardiovascular disease [7]. Hypoglycemic episodes also elevate the risk of falls, which can result in fractures, head injuries, emergency department visits, and long-term health decline [8]. Additionally, recurrent hypoglycemia can impair cognitive and physical function, diminish quality of life, reduce adherence to treatment regimens, and exacerbate frailty [9].

Because the risk of hypoglycemia increases with more stringent glycemic targets, careful consideration is necessary when setting glycemic control goals. Individualized treatment plans should aim to balance effective blood glucose management with minimizing the risk of hypoglycemic events to ensure the safety and well-being of older adults.

GLUCOSE-LOWERING MEDICATIONS

Pharmacological management of type 2 diabetes mellitus in older adults requires careful consideration of various factors to ensure both efficacy and safety. Below is a detailed overview of commonly used glucose-lowering medications, including their advantages and disadvantages (Table 1).

Metformin

Metformin is the recommended first-line therapy for type 2 diabetes mellitus, including in older adults [1]. It effectively lowers blood glucose levels and carries a low risk of hypoglycemia. Common side effects include appetite loss, nausea, diarrhea, and a metallic taste. Given that gastrointestinal symptoms such as loss of appetite can significantly diminish quality of life in older adults, it is crucial to monitor them closely for these symptoms. Extended-release formulations are often better tolerated due to fewer gastrointestinal symptoms. Since gastrointestinal side effects are more common at higher doses, it is advisable to start with a low dose and gradually increase every 2 to 3 weeks based on glucose monitoring.

Metformin may also impair the absorption of vitamin B12 and folic acid. It is suggested that 5.8% to 33% of people taking metformin may develop a vitamin B12 deficiency [10,11]. Close monitoring of vitamin B12 deficiency is advised in older adults, especially in patients with atrophic gastritis or unexplained anemia [12].

Lactic acidosis is a very rare but potentially life-threatening side effect of metformin. Therefore, metformin should not be used in conditions where lactic acid production is increased, or its excretion is decreased including kidney disease, liver disease, alcoholism, congestive heart failure, peripheral vascular disease, and obstructive pulmonary disease. Special caution is warranted in older adults, who are more likely to have these conditions. Metformin can be used in patients with stable heart failure but should be avoided in those who are hospitalized for heart failure or have uncontrolled heart failure. Metformin is contraindicated in cases of severe liver dysfunction or kidney dysfunction. It should be used with caution if the estimated glomerular filtration rate (eGFR) is less than 45 mL/min/1.73 m² and is contraindicated if the eGFR is less than 30 mL/min/1.73 m². Metformin administration should be stopped immediately in the event of dehydration, hypoxia, or sepsis.

Thiazolidinediones

TZDs (e.g., pioglitazone, lobeglitazone) are insulin sensitizers that are liver-metabolized and excreted via bile allowing for unchanged dosages in patients with impaired kidney function. They are contraindicated in individuals with active liver disease or those whose liver enzyme levels are elevated to 2.5 times above the normal range. TZDs offer the benefits of once-daily dosing and carry no risk of hypoglycemia. Despite these advantages, their use in older patients is limited due to potential risks such as weight gain, edema, exacerbation of heart failure, fractures, and concerns regarding bladder cancer stability [13]. TZDs are specifically contraindicated in patients with New York Heart Association class III and IV congestive heart failure [1]. Additionally, TZDs have been shown to increase bone loss and raise the risk of fractures in older women [14,15]. Given that the risk of fractures is already heightened in individuals with type 2 diabetes mellitus due to increased fall risks, localized bone loss, and impaired bone quality, TZDs should be prescribed cautiously in patients who are at risk for osteoporosis.

Sulfonylureas

Sulfonylureas are cost-effective and potent but are associated with a higher risk of hypoglycemia and weight gain. In older patients with diabetes mellitus, sulfonylureas should be prescribed with caution, starting at the lowest effective dose to minimize the risk of hypoglycemia. In patients with stage 3 or higher chronic kidney disease, glyburide (glibenclamide) is contraindicated, glimepiride should be initiated at a low dose, and glipizide and gliclazide can generally be used without dose adjustments. These medications should only be considered if the patient consistently consumes regular meals, can recognize the symptoms of hypoglycemia, and can manage hypoglycemia appropriately. Short-acting sulfonylureas are preferred in this population. Among sulfonylureas, gliclazide is noted for its lower risk of hypoglycemia in older patients [16].

Meglitinides

Although meglitinides have a lower risk of hypoglycemia compared to sulfonylureas [17,18], they can still cause hypoglycemia and weight gain. The requirement to take these medications 2 to 3 times daily with meals may be inconvenient; however, their administration can be skipped if a meal is missed, reducing the risk of hypoglycemia. This feature makes meglitinides particularly beneficial for older patients with diabetes mellitus who have irregular meal schedules.

Repaglinide is a suitable option for patients with severely reduced kidney function, as it does not require significant dose adjustments. Nateglinide, on the other hand, is appropriate for patients with an eGFR of 30 mL/min/1.73 m² or higher, but dose adjustments are necessary in this population.

Dipeptidyl peptidase-4 inhibitors

Dipeptidyl peptidase-4 (DPP4) inhibitors are effective for glycemic control, especially managing postprandial blood glucose levels and have a very low risk of hypoglycemia [19–22]. When used as monotherapy, they rarely cause hypoglycemia; however, the risk increases when combined with insulin or sulfonylureas. Therefore, it is recommended to reduce the dosage of insulin or sulfonylureas in advance or provide patient education on recognizing and managing hypoglycemia when it is added to insulin or sulfonylureas.

Unlike other insulin secretagogues, DPP4 inhibitors do not cause weight gain and are associated with minimal side effects, making them increasingly popular and widely used in recent years. They are considered safe and effective for older patients with diabetes mellitus. Although DPP4 inhibitors can be used safely in patients with reduced kidney function, dosage adjustments may be necessary for some medications. While these drugs are generally considered safe for patients with cardiovascular diseases, a prospective study assessing cardiovascular safety in high-risk patients revealed that saxagliptin might increase the risk of hospitalization for heart failure [23]. Consequently, saxagliptin is not recommended for people with a history of heart failure. Given the high prevalence of heart failure among older patients with diabetes mellitus, additional vigilance is necessary when prescribing saxagliptin in this population.

Glucagon-like peptide-1 receptor agonists

The safety and efficacy of glucagon-like peptide-1 (GLP-1) receptor agonists have been well-established in studies involving older patients with diabetes mellitus [24–26]. These medications are associated with a low risk of hypoglycemia and offer the added benefit of promoting weight loss. In the LEADER study, which evaluated cardiovascular safety, liraglutide significantly reduced both the incidence and mortality rates of major cardiovascular events, making it the first GLP-1 receptor agonist to achieve such outcomes [27]. Similarly, the SUSTAIN-6 study demonstrated that semaglutide significantly reduced the incidence of cardiovascular events [28].

Although GLP-1 receptor agonists rarely cause hypoglycemia when used as monotherapy, the risk may increase when combined with other hypoglycemia-inducing medications. A key limitation of these drugs is that they are administered via injection (oral semaglutide is currently not available in Korea), and they may cause gastrointestinal side effects, including nausea, vomiting, and diarrhea. Before initiating treatment, it is important to ensure that the patient has adequate vision, motor skills, and cognitive capacity to manage injections safely. Short-acting GLP-1 receptor agonists are more likely to cause nausea and vomiting. Starting at the lowest dose and gradually increasing it can help mitigate gastrointestinal side effects.

Caution is advised when prescribing GLP-1 receptor agonists to older adults, as significant weight loss or persistent gastrointestinal symptoms could adversely impact their quality of life.

Αlpha-glucosidase inhibitors

Alpha-glucosidase inhibitors provide effective postprandial glycemic control and carry a very low risk of hypoglycemia. Their efficacy and safety have been validated in older adults [29,30]. However, these medications require multiple daily doses and may cause gastrointestinal side effects, such as abdominal distension, diarrhea, and frequent flatulence. Initiating treatment with a low dose and gradually increasing it in small increments can help minimize these adverse effects.

These drugs are contraindicated in patients with inflammatory bowel disease, a creatinine level of 2.0 mg/dL or higher, or liver cirrhosis. When used as monotherapy, alpha-glucosidase inhibitors do not induce hypoglycemia, weight gain, or hyperinsulinemia. However, if hypoglycemia occurs during combination therapy with sulfonylureas or insulin, recovery may be delayed despite oral carbohydrate intake. In such cases, consuming pure glucose (dextrose) is recommended to expedite recovery from hypoglycemia. Patient education on this specific aspect of treatment is essential to ensure safe and effective management.

SGLT2 inhibitors

SGLT2 inhibitors lower blood glucose levels by inhibiting glucose reabsorption in the renal tubules through SGLT2, leading to increased glucose excretion via urine. SGLT2 inhibitors are generally well tolerated and effective for glycemic control in older adults with type 2 diabetes [31–33].

Additional beneficial effects of SGLT2 inhibitors on reducing hospitalizations for heart failure and improving renal outcomes also have been shown from subsequent studies designed to evaluate cardiovascular and renal safety [34–36]. These benefits have also been observed in subanalyses focusing on individuals aged 65 years and older, suggesting a priority in their use among older patients with diabetes who have cardiovascular disease [37].

SGLT2 inhibitors operate independently of insulin and do not increase insulin secretion, thus presenting a very low risk of hypoglycemia. However, when used in conjunction with medications that have a high risk of hypoglycemia, such as insulin or insulin secretagogues, dose adjustments may be necessary to prevent hypoglycemic episodes.

The use of SGLT2 inhibitors leads to increased urinary glucose excretion, which can raise the risk of urinary tract or genital infections. Additionally, the osmotic diuresis induced by these drugs can cause fluid depletion, potentially leading to dehydration, orthostatic hypotension, electrolyte imbalances, and increased hematocrit. Despite these side effects, they are not known to adversely affect patients' quality of life in clinical practice. Nevertheless, caution is advised in individuals aged 75 years and older or those taking diuretics [38].

Euglycemic diabetic ketoacidosis, a condition that may occur at low blood glucose levels, has been reported with the use of SGLT2 inhibitors [39,40], and this risk also exists in older adults with type 2 diabetes mellitus [41]. Symptoms such as dyspnea, nausea, vomiting, and abdominal pain should be monitored closely.

SGLT2 inhibitors might lead to skeletal muscle loss alongside reductions in body weight and fat mass. The potential of SGLT2 inhibitors to cause sarcopenia remains unconfirmed; however, caution is advised in older patients with type 2 diabetes mellitus particularly at risk of exacerbated sarcopenia. Ongoing clinical studies aim to further explore this issue [42].

Insulins

Patients with type 2 diabetes mellitus often initiate insulin therapy after unsuccessful attempts with oral hypoglycemic agents, making insulin a common treatment among older individuals who have had diabetes for an extended period.

Educating elderly patients and their caregivers on insulin and injectable therapies requires tailored strategies that account for age-related challenges such as cognitive decline, visual impairments, and limited manual dexterity. Before starting insulin therapy in older patients, it is crucial to assess whether the patient or their caregiver has impairments in vision, motor skills, or cognitive function [1,43–45]. If cognitive issues such as memory loss or dementia are present, these must be taken into account when providing instructions. It is important to use short, clear sentences, avoid overwhelming the listener with too much information at once, and frequently repeat key points to reinforce understanding. Additionally, caregivers should be actively involved in the education process to ensure proper support in daily insulin administration. Elderly patients may face challenges such as hearing loss, visual impairments, or reduced hand strength. For hearing impairments, it is important to speak slowly and clearly, or use written instructions. For visual impairments, large-print materials and high-contrast designs can be helpful. If manual dexterity is an issue, teaching specific techniques or recommending devices that are easier to handle, such as pens with larger grips, can improve their ability to administer insulin.

Given that insulin therapy poses a higher risk of hypoglycemia compared to other medications, it is prudent to establish a blood glucose target that minimizes the risk of hypoglycemia. This involves simplifying the treatment regimen, starting with a low dose, and gradually titrating upward. Basal insulin, administered once daily, is the preferred option. In contrast, multiple-dose insulin therapy, which is more complex, should be avoided in older patients with advanced complications or reduced physical function. Among basal insulins, insulin glargine U300 and insulin degludec are associated with a lower incidence of hypoglycemia in older adults compared to insulin glargine U100 [46,47].

For older adults in long-term care facilities, who often have multiple comorbidities and varying life expectancies, it is essential to tailor treatment goals and approaches to the individual. Generally, overly strict glycemic control is not recommended. Instead, management should aim to maintain blood glucose levels that prevent symptoms of hyperglycemia, such as dehydration, infections, and urinary incontinence, while avoiding hypoglycemia. Additionally, self-monitoring of blood glucose should be minimized to preserve quality of life.

CONCLUSIONS

Pharmacological treatment of diabetes mellitus in older adults necessitates a personalized approach, balancing glycemic control with minimizing hypoglycemia risk. Factors such as life expectancy, comorbidities, frailty, and cognitive ability must be assessed. Starting with monotherapy and gradually adjusting dosages ensures safety and efficacy. Ongoing monitoring for drug interactions, side effects, and treatment adherence is essential to optimize outcomes and maintain quality of life in this vulnerable population.

ARTICLE INFORMATION

Conflicts of interest

Junghyun Noh is the editor-in-chief of this journal, but was not involved in the peer reviewer selection, evaluation, or decision process of this article. The author has no other conflicts of interest to declare.

Funding

The author received no financial support for this study.

REFERENCES

• 1. Moon JS, Kang S, Choi JH, Lee KA, Moon JH, Chon S, et al. 2023 Clinical Practice Guidelines for diabetes management in Korea: full version recommendation of the Korean Diabetes Association. Diabetes Metab J 2024;48:546–708. ArticlePubMedPMCPDF
• 2. Alagiakrishnan K, Sclater A. Psychiatric disorders presenting in the elderly with type 2 diabetes mellitus. Am J Geriatr Psychiatry 2012;20:645–52. ArticlePubMed
• 3. Ponticelli C, Sala G, Glassock RJ. Drug management in the elderly adult with chronic kidney disease: a review for the primary care physician. Mayo Clin Proc 2015;90:633–45. ArticlePubMed
• 4. Wong CW. Avoiding hypoglycaemia: a new target of care for elderly diabetic patients. Hong Kong Med J 2015;21:444–54. ArticlePubMed
• 5. Lipska KJ, Ross JS, Wang Y, Inzucchi SE, Minges K, Karter AJ, et al. National trends in US hospital admissions for hyperglycemia and hypoglycemia among Medicare beneficiaries, 1999 to 2011. JAMA Intern Med 2014;174:1116–24. ArticlePubMedPMC
• 6. Yang SW, Park KH, Zhou YJ. The impact of hypoglycemia on the cardiovascular system: physiology and pathophysiology. Angiology 2016;67:802–9. ArticlePubMedPDF
• 7. Davis SN, Duckworth W, Emanuele N, Hayward RA, Wiitala WL, Thottapurathu L, et al. Effects of severe hypoglycemia on cardiovascular outcomes and death in the Veterans Affairs Diabetes Trial. Diabetes Care 2019;42:157–63. ArticlePubMedPMCPDF
• 8. Zhao Y, Kachroo S, Kawabata H, Colilla S, Mukherjee J, Fonseca V, et al. Association between hypoglycemia and fall-related fractures and health care utilization in older veterans with type 2 diabetes. Endocr Pract 2016;22:196–204. ArticlePubMed
• 9. Ye M, Yang Q, Zhang L, Song H, Fu Q, Qian J, et al. Effect of hypoglycemic events on cognitive function in individuals with type 2 diabetes mellitus: a dose-response meta-analysis. Front Neurol 2024;15:1394499.ArticlePubMedPMC
• 10. Ko SH, Ko SH, Ahn YB, Song KH, Han KD, Park YM, et al. Association of vitamin B12 deficiency and metformin use in patients with type 2 diabetes. J Korean Med Sci 2014;29:965–72. ArticlePubMedPMCPDF
• 11. Yang W, Cai X, Wu H, Ji L. Associations between metformin use and vitamin B12 levels, anemia, and neuropathy in patients with diabetes: a meta-analysis. J Diabetes 2019;11:729–43. ArticlePubMedPDF
• 12. Leung S, Mattman A, Snyder F, Kassam R, Meneilly G, Nexo E. Metformin induces reductions in plasma cobalamin and haptocorrin bound cobalamin levels in elderly diabetic patients. Clin Biochem 2010;43:759–60. Article
• 13. Kahn SE, Haffner SM, Heise MA, Herman WH, Holman RR, Jones NP, et al. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med 2006;355:2427–43. ArticlePubMed
• 14. Loke YK, Singh S, Furberg CD. Long-term use of thiazolidinediones and fractures in type 2 diabetes: a meta-analysis. CMAJ 2009;180:32–9. ArticlePubMedPMC
• 15. Schwartz AV, Chen H, Ambrosius WT, Sood A, Josse RG, Bonds DE, et al. Effects of TZD use and discontinuation on fracture rates in ACCORD Bone Study. J Clin Endocrinol Metab 2015;100:4059–66. ArticlePubMedPMC
• 16. Schernthaner G, Grimaldi A, Di Mario U, Drzewoski J, Kempler P, Kvapil M, et al. GUIDE study: double-blind comparison of once-daily gliclazide MR and glimepiride in type 2 diabetic patients. Eur J Clin Invest 2004;34:535–42. Article
• 17. Del Prato S, Heine RJ, Keilson L, Guitard C, Shen SG, Emmons RP. Treatment of patients over 64 years of age with type 2 diabetes: experience from nateglinide pooled database retrospective analysis. Diabetes Care 2003;26:2075–80. ArticlePubMed
• 18. Papa G, Fedele V, Rizzo MR, Fioravanti M, Leotta C, Solerte SB, et al. Safety of type 2 diabetes treatment with repaglinide compared with glibenclamide in elderly people: a randomized, open-label, two-period, cross-over trial. Diabetes Care 2006;29:1918–20. ArticlePubMed
• 19. Schernthaner G, Barnett AH, Patel S, Hehnke U, von Eynatten M, Woerle HJ. Safety and efficacy of the dipeptidyl peptidase-4 inhibitor linagliptin in elderly patients with type 2 diabetes: a comprehensive analysis of data from 1331 individuals aged ≥ 65 years. Diabetes Obes Metab 2014;16:1078–86. ArticlePubMed
• 20. Round EM, Engel SS, Golm GT, Davies MJ, Kaufman KD, Goldstein BJ. Safety of sitagliptin in elderly patients with type 2 diabetes: a pooled analysis of 25 clinical studies. Drugs Aging 2014;31:203–14. ArticlePDF
• 21. Karyekar CS, Ravichandran S, Allen E, Fleming D, Frederich R. Tolerability and efficacy of glycemic control with saxagliptin in older patients (aged ≥ 65 years) with inadequately controlled type 2 diabetes mellitus. Clin Interv Aging 2013;8:419–30. ArticlePubMedPMC
• 22. Schwartz SL. Treatment of elderly patients with type 2 diabetes mellitus: a systematic review of the benefits and risks of dipeptidyl peptidase-4 inhibitors. Am J Geriatr Pharmacother 2010;8:405–18. ArticlePubMed
• 23. Leiter LA, Teoh H, Braunwald E, Mosenzon O, Cahn A, Kumar KM, et al. Efficacy and safety of saxagliptin in older participants in the SAVOR-TIMI 53 trial. Diabetes Care 2015;38:1145–53. ArticlePubMedPDF
• 24. Bode BW, Brett J, Falahati A, Pratley RE. Comparison of the efficacy and tolerability profile of liraglutide, a once-daily human GLP-1 analog, in patients with type 2 diabetes ≥65 and <65 years of age: a pooled analysis from phase III studies. Am J Geriatr Pharmacother 2011;9:423–33. ArticlePubMed
• 25. Boustani MA, Pittman I 4th, Yu M, Thieu VT, Varnado OJ, Juneja R. Similar efficacy and safety of once-weekly dulaglutide in patients with type 2 diabetes aged ≥65 and <65 years. Diabetes Obes Metab 2016;18:820–8. ArticlePubMedPMCPDF
• 26. Meneilly GS, Roy-Duval C, Alawi H, Dailey G, Bellido D, Trescoli C, et al. Lixisenatide therapy in older patients with type 2 diabetes inadequately controlled on their current antidiabetic treatment: the GetGoal-O randomized trial. Diabetes Care 2017;40:485–93. ArticlePubMedPDF
• 27. Marso SP, Daniels GH, Brown-Frandsen K, Kristensen P, Mann JF, Nauck MA, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2016;375:311–22. Article
• 28. Marso SP, Bain SC, Consoli A, Eliaschewitz FG, Jodar E, Leiter LA, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med 2016;375:1834–44. ArticlePubMed
• 29. Johnston PS, Lebovitz HE, Coniff RF, Simonson DC, Raskin P, Munera CL. Advantages of alpha-glucosidase inhibition as monotherapy in elderly type 2 diabetic patients. J Clin Endocrinol Metab 1998;83:1515–22. ArticlePubMed
• 30. Josse RG, Chiasson JL, Ryan EA, Lau DC, Ross SA, Yale JF, et al. Acarbose in the treatment of elderly patients with type 2 diabetes. Diabetes Res Clin Pract 2003;59:37–42. ArticlePubMed
• 31. Sinclair AJ, Bode B, Harris S, Vijapurkar U, Shaw W, Desai M, et al. Efficacy and safety of canagliflozin in individuals aged 75 and older with type 2 diabetes mellitus: a pooled analysis. J Am Geriatr Soc 2016;64:543–52. ArticlePDF
• 32. Lunati ME, Cimino V, Gandolfi A, Trevisan M, Montefusco L, Pastore I, et al. SGLT2-inhibitors are effective and safe in the elderly: the SOLD study. Pharmacol Res 2022;183:106396.ArticlePubMed
• 33. Fioretto P, Mansfield TA, Ptaszynska A, Yavin Y, Johnsson E, Parikh S. Long-term safety of dapagliflozin in older patients with type 2 diabetes mellitus: a pooled analysis of phase IIb/III studies. Drugs Aging 2016;33:511–22. ArticlePubMedPMCPDF
• 34. Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 2015;373:2117–28. ArticlePubMed
• 35. Neal B, Perkovic V, Mahaffey KW, de Zeeuw D, Fulcher G, Erondu N, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med 2017;377:644–57. Article
• 36. Wiviott SD, Raz I, Bonaca MP, Mosenzon O, Kato ET, Cahn A, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2019;380:347–57. Article
• 37. Pratley RE, Cannon CP, Cherney DZ, Cosentino F, McGuire DK, Essex MN, et al. Cardiorenal outcomes, kidney function, and other safety outcomes with ertugliflozin in older adults with type 2 diabetes (VERTIS CV): secondary analyses from a randomised, double-blind trial. Lancet Healthy Longev 2023;4:e143–54. ArticlePubMed
• 38. Jeon JY, Kim DJ. Benefit and safety of sodium-glucose co-transporter 2 inhibitors in older patients with type 2 diabetes mellitus. Diabetes Metab J 2024;48:837–46. ArticlePubMedPMCPDF
• 39. Erondu N, Desai M, Ways K, Meininger G. Diabetic ketoacidosis and related events in the canagliflozin type 2 diabetes clinical program. Diabetes Care 2015;38:1680–6. ArticlePubMedPMCPDF
• 40. Peters AL, Buschur EO, Buse JB, Cohan P, Diner JC, Hirsch IB. Euglycemic diabetic ketoacidosis: a potential complication of treatment with sodium-glucose cotransporter 2 inhibition. Diabetes Care 2015;38:1687–93. ArticlePubMedPMCPDF
• 41. Rigato M, Fadini GP, Avogaro A. Safety of sodium-glucose cotransporter 2 inhibitors in elderly patients with type 2 diabetes: a meta-analysis of randomized controlled trials. Diabetes Obes Metab 2023;25:2963–9. ArticlePubMed
• 42. Yabe D, Shiki K, Suzaki K, Meinicke T, Kotobuki Y, Nishida K, et al. Rationale and design of the EMPA-ELDERLY trial: a randomised, double-blind, placebo-controlled, 52-week clinical trial of the efficacy and safety of the sodium-glucose cotransporter-2 inhibitor empagliflozin in elderly Japanese patients with type 2 diabetes. BMJ Open 2021;11:e045844. ArticlePubMedPMC
• 43. American Diabetes Association Professional Practice Committee. 13. Older adults: standards of care in diabetes: 2025. Diabetes Care 2025;48(Supplement_1):S266–82.Article
• 44. Trimble LA, Sundberg S, Markham L, Janicijevic S, Beattie BL, Meneilly GS. Value of the clock drawing test to predict problems with insulin skills in older adults. Can J Diabetes 2005;29:102–4.
• 45. Zeyfang A, Berndt S, Aurnhammer G, Nikolaus T, Oster P, Bahrmann A. A short easy test can detect ability for autonomous insulin injection by the elderly with diabetes mellitus. J Am Med Dir Assoc 2012;13:81.ArticlePubMed
• 46. Ritzel R, Roussel R, Bolli GB, Vinet L, Brulle-Wohlhueter C, Glezer S, et al. Patient-level meta-analysis of the EDITION 1, 2 and 3 studies: glycaemic control and hypoglycaemia with new insulin glargine 300 U/ml versus glargine 100 U/ml in people with type 2 diabetes. Diabetes Obes Metab 2015;17:859–67. ArticlePubMedPMC
• 47. Sorli C, Warren M, Oyer D, Mersebach H, Johansen T, Gough SC. Elderly patients with diabetes experience a lower rate of nocturnal hypoglycaemia with insulin degludec than with insulin glargine: a meta-analysis of phase IIIa trials. Drugs Aging 2013;30:1009–18. ArticlePubMedPMCPDF

Figure & Data

References

Citations

Citations to this article as recorded by  

• Medication Use Patterns, Polypharmacy, and Potentially Inappropriate Medications among Institutionalized Older Adults in East Coast Malaysia: A Cross-sectional Study
  Azlini Ismail, Basma Ezzat Mustafa, Farah Natashah Mohd, Muhd Firdaus Che Musa, Nazih Shaban Mustafa, Khairani Idah Mokhtar, Yunita Dewi Ardini, Omar Abdul Jabbar Abdul Qader
  Journal of Research in Pharmacy Practice.2026;[Epub]     CrossRef
• Unlocking the dual healing powers of plant-based metallic nanoparticles: managing diabetes and tackling male infertility challenges
  Ayesha Siddiqa, Rahmatullah Qureshi, Ghazala Yasmin, Shaista Rafique, Noor-Ul-Ain Zafar, Chudary Sadam Hussain, Sana ur Rehman, Neelum Naheed
  Frontiers in Endocrinology.2025;[Epub]     CrossRef
• SITAGLIPTIN IN TYPE 2 DIABETES MANAGEMENT: A STUDY OF ADD ON THERAPY IN BALI, INDONESIA
  ANAK AGUNG KETUT PURNAMA SARI, PHEBE HENDRA, DITA MARIA VIRGINIA
  Asian Journal of Pharmaceutical and Clinical Research.2025; : 115.     CrossRef