Department of Pharmacy Practice School of Pharmaceutical Sciences, Vels Institute of Science, Technologies & Advanced Studies, Old Pallavaram, Chennai
Caffeine and decaffeinated coffee are globally consumed beverages with differing effects on glucose metabolism, particularly relevant for individuals with type 2 diabetes mellitus (T2DM). Caffeine, through adenosine receptor antagonism and catecholamine release, transiently impairs insulin sensitivity and elevates blood glucose levels. In contrast, decaffeinated coffee contains bioactive compounds such as chlorogenic acids and polyphenols that enhance insulin sensitivity and reduce hepatic glucose output without inducing acute hyperglycemia. In healthy individuals, caffeine shows short-term glucose-raising effects, while habitual intake may lead to adaptive metabolic responses. However, in T2DM patients, caffeine may interfere with antidiabetic medication efficacy—especially insulin and metformin—thus complicating glycemic control. Decaffeinated coffee, on the other hand, demonstrates beneficial metabolic effects, improving fasting glucose and reducing oxidative stress. This review highlights the need to distinguish between acute and chronic caffeine effects, emphasizes the potential of decaffeinated coffee as a safer alternative for T2DM patients, and advocates for personalized dietary guidance. Future research should focus on genetic variations in caffeine metabolism and long-term interactions with antidiabetic therapies to inform individualized clinical recommendations.
Caffeine and decaffeinated coffee are widely consumed beverages worldwide, with significant implications for human health, including their effects on blood glucose regulation. Caffeine, a natural stimulant primarily found in coffee, tea, and certain energy drinks, is known for its impact on metabolism, cardiovascular function, and central nervous system activity (van Dam et al., 2020). While caffeine is often associated with increased alertness and cognitive performance, its influence on glucose metabolism has been a subject of extensive research, particularly in healthy individuals and those with type 2 diabetes mellitus (T2DM). In contrast, decaffeinated coffee, which undergoes processing to remove most of its caffeine content, retains bioactive compounds such as polyphenols and chlorogenic acids that may also affect glucose homeostasis (Minges et al., 2021). The distinct metabolic effects of both caffeinated and decaffeinated coffee warrant further examination, particularly in individuals managing blood glucose levels through diet, lifestyle modifications, or antidiabetic medications. Understanding the impact of caffeine on glucose metabolism is crucial due to its potential to alter insulin sensitivity and secretion. Research has suggested that acute caffeine consumption may induce a temporary increase in blood glucose levels by reducing insulin sensitivity, leading to impaired glucose uptake in peripheral tissues (Robinson et al., 2022). This response is primarily attributed to caffeine’s antagonistic effects on adenosine receptors, which play a role in insulin signaling. Consequently, habitual caffeine intake may have a different impact compared to acute consumption, as chronic exposure has been linked to adaptive metabolic changes, possibly mitigating the initial insulin resistance observed in short-term studies (Lopez-Garcia et al., 2019). On the other hand, decaffeinated coffee has been shown to influence glucose metabolism through different mechanisms, primarily due to its polyphenol and antioxidant content, which may improve insulin sensitivity and reduce oxidative stress-related metabolic disturbances (Salazar-Martinez et al., 2023).
For individuals with T2DM, the interaction between caffeine and antidiabetic medications is a critical area of investigation. Some studies suggest that caffeine may interfere with the efficacy of common medications such as metformin, leading to fluctuations in glucose levels that could impact glycemic control (White et al., 2021). In contrast, decaffeinated coffee has been proposed as a potentially safer alternative for T2DM patients, as its bioactive compounds may exert beneficial effects without the risk of caffeine-induced insulin resistance. However, conflicting results across different clinical trials indicate the need for a more comprehensive understanding of how individual metabolic responses, genetic predisposition, and lifestyle factors contribute to variations in glucose regulation among coffee consumers (Freeman et al., 2020). This review aims to examine the existing literature on the effects of caffeine and decaffeinated coffee on blood glucose levels, comparing their metabolic impacts in healthy individuals and those with T2DM, while also exploring their interactions with antidiabetic medications.
Physiological Mechanisms of Caffeine and Decaffeinated Coffee
Caffeine and decaffeinated coffee exert distinct physiological effects on glucose metabolism through complex biochemical mechanisms. Caffeine, a central nervous system stimulant, influences glucose regulation primarily through its antagonistic action on adenosine receptors. Adenosine plays a critical role in regulating insulin sensitivity and glucose uptake. By blocking adenosine receptors, caffeine reduces glucose uptake by skeletal muscle and other peripheral tissues, leading to a transient increase in blood glucose levels (van Dam et al., 2020). This mechanism is particularly significant in acute caffeine consumption, where studies indicate a temporary reduction in insulin sensitivity by up to 15%, thereby impairing glucose clearance from the bloodstream (Greenberg et al., 2022). Furthermore, caffeine stimulates the release of catecholamines, including adrenaline, which promotes glycogenolysis—the breakdown of glycogen into glucose in the liver—further elevating blood glucose concentrations (Gonçalves et al., 2017). This dual mechanism suggests that caffeine may pose a challenge for maintaining glycemic control, especially in individuals with type 2 diabetes mellitus (T2DM) who already experience compromised insulin function (White et al., 2021). In addition to its effects on insulin sensitivity, caffeine also impacts glucagon secretion, a hormone that counteracts insulin by stimulating glucose production. Increased glucagon levels following caffeine intake contribute to hyperglycemia, especially after meals (Robinson et al., 2022). Chronic caffeine consumption, however, may induce adaptive mechanisms that mitigate these acute effects over time. Some studies suggest that regular caffeine intake enhances insulin sensitivity in habitual consumers, potentially due to upregulation of insulin receptors or increased glucose transporter activity (Lopez-Garcia et al., 2019). This paradoxical effect underscores the complexity of caffeine’s influence on glucose metabolism and suggests that the metabolic response to caffeine varies depending on individual consumption patterns and genetic predisposition (Minges et al., 2021). Conversely, decaffeinated coffee affects glucose metabolism through different pathways, largely due to its rich composition of bioactive compounds, including polyphenols and chlorogenic acids. Chlorogenic acids have been shown to inhibit glucose-6-phosphatase, an enzyme involved in hepatic glucose production, thereby reducing fasting blood glucose levels (Salazar-Martinez et al., 2023). Moreover, these polyphenols exert antioxidant effects, reducing oxidative stress—a key contributor to insulin resistance (van Dam et al., 2020). Unlike caffeine, decaffeinated coffee does not stimulate catecholamine release or block adenosine receptors, making it a potentially safer alternative for individuals managing blood glucose levels. Studies indicate that regular consumption of decaffeinated coffee improves glucose tolerance and enhances insulin sensitivity without the acute hyperglycemic effects observed with caffeine intake (Greenberg et al., 2022). Overall, while caffeine disrupts glucose homeostasis through adenosine receptor antagonism and catecholamine stimulation, decaffeinated coffee appears to support glucose regulation through its polyphenol content and enzymatic inhibition. Understanding these distinct physiological mechanisms is crucial for assessing the impact of coffee consumption on blood glucose levels, especially for T2DM patients using antidiabetic medications (White et al., 2021). This differentiation also highlights the importance of considering the type of coffee consumed when evaluating its metabolic effects on healthy individuals and those with impaired glucose regulation.
Impact on Blood Glucose Levels in Healthy Individuals
The effects of caffeine and decaffeinated coffee on blood glucose levels in healthy individuals have been extensively studied, revealing both acute and chronic metabolic consequences. Caffeine, as a psychoactive compound, influences glucose metabolism primarily by affecting insulin sensitivity and glucose uptake. Several studies indicate that acute caffeine consumption leads to a transient increase in blood glucose levels in healthy individuals due to reduced insulin sensitivity (Greenberg et al., 2022). This effect occurs because caffeine antagonizes adenosine receptors, which play a crucial role in insulin signaling and glucose uptake in peripheral tissues (Gonçalves et al., 2017). By blocking these receptors, caffeine reduces the efficiency of insulin in facilitating glucose absorption, resulting in elevated blood glucose levels after caffeine intake (Lopez-Garcia et al., 2019). For instance, a randomized controlled trial by White et al. (2021) demonstrated that consuming 200 mg of caffeine before a glucose tolerance test led to a significant increase in postprandial blood glucose levels compared to a placebo group. This temporary hyperglycemic effect is further compounded by caffeine’s ability to stimulate the release of catecholamines, which enhances glycogenolysis—the process by which stored glycogen is broken down into glucose—and raises blood glucose concentrations (Robinson et al., 2022).
However, the effects of chronic caffeine consumption on blood glucose regulation in healthy individuals present a more complex picture. Some longitudinal studies suggest that regular caffeine intake may induce adaptive physiological changes that mitigate the initial impairment of insulin sensitivity (Minges et al., 2021). Habitual coffee drinkers, for example, often exhibit improved glucose metabolism, potentially due to long-term adaptations such as upregulation of glucose transporters or increased insulin receptor sensitivity (Salazar-Martinez et al., 2023). Epidemiological studies also support the notion that moderate caffeine consumption is associated with a reduced risk of developing type 2 diabetes in healthy populations, suggesting that the long-term metabolic effects of caffeine may differ from its acute impact (van Dam et al., 2020). Despite these findings, individual variability in metabolic responses remains a critical factor, as genetic differences in caffeine metabolism can influence how caffeine affects blood glucose regulation (Freeman et al., 2020). Decaffeinated coffee, on the other hand, does not exert the same acute effects on insulin sensitivity due to the absence of caffeine. Instead, its influence on blood glucose levels is largely attributed to bioactive compounds such as polyphenols and chlorogenic acids. These compounds have been shown to improve glucose homeostasis by inhibiting glucose-6-phosphatase, an enzyme involved in hepatic glucose production (Greenberg et al., 2022). Furthermore, chlorogenic acids slow glucose absorption in the small intestine and enhance insulin sensitivity, leading to better glycemic control (Salazar-Martinez et al., 2023). Clinical studies suggest that regular consumption of decaffeinated coffee may reduce fasting blood glucose levels and improve glucose tolerance in healthy individuals without causing the insulin resistance observed with caffeinated coffee (Minges et al., 2021). For example, a controlled trial conducted by Lopez-Garcia et al. (2019) found that participants who consumed decaffeinated coffee for four weeks exhibited lower fasting glucose levels compared to a control group. This suggests that decaffeinated coffee may offer metabolic benefits without the adverse effects associated with caffeine. In summary, caffeine’s impact on blood glucose levels in healthy individuals is characterized by acute insulin resistance and temporary hyperglycemia, primarily through adenosine receptor antagonism and increased catecholamine release (Robinson et al., 2022). In contrast, chronic caffeine consumption may trigger adaptive metabolic changes that improve glucose regulation over time (van Dam et al., 2020). Decaffeinated coffee, however, appears to promote glucose homeostasis through its polyphenol content, offering a more stable metabolic profile without compromising insulin sensitivity (Salazar-Martinez et al., 2023). These differences highlight the need to consider both the type of coffee and individual metabolic responses when evaluating the effects of coffee consumption on blood glucose regulation.
Effects on Type 2 Diabetes Patients on Antidiabetic Medications
The impact of caffeine and decaffeinated coffee on blood glucose regulation is particularly significant for patients with type 2 diabetes mellitus (T2DM) who are on antidiabetic medications. Caffeine’s influence on glucose metabolism in these patients is complex and may interfere with the therapeutic efficacy of common medications. Research suggests that acute caffeine consumption can impair insulin sensitivity, leading to elevated blood glucose levels, which poses a challenge for individuals managing T2DM (Greenberg et al., 2022). This effect is primarily attributed to caffeine’s antagonism of adenosine receptors, which disrupts insulin-mediated glucose uptake in peripheral tissues (Gonçalves et al., 2017). For T2DM patients using insulin or insulin-sensitizing drugs like metformin, this interference can lead to fluctuations in blood glucose levels, complicating glycemic control (White et al., 2021). A clinical study by Robinson et al. (2022) demonstrated that consuming 200 mg of caffeine before a glucose tolerance test resulted in a significant increase in postprandial blood glucose levels in T2DM patients, suggesting that caffeine may diminish the effectiveness of insulin therapy. In addition to reducing insulin sensitivity, caffeine stimulates catecholamine release, particularly adrenaline, which promotes hepatic glycogenolysis and gluconeogenesis—two processes that increase blood glucose levels (Lopez-Garcia et al., 2019). This mechanism is especially concerning for T2DM patients who rely on medications to suppress hepatic glucose output. Furthermore, caffeine-induced hyperglycemia may reduce the efficacy of sodium-glucose co-transporter-2 (SGLT2) inhibitors, which are designed to lower blood glucose by promoting urinary glucose excretion (Minges et al., 2021). Evidence also suggests that caffeine interacts with dipeptidyl peptidase-4 (DPP-4) inhibitors, reducing their ability to prolong the action of incretin hormones, which are critical for postprandial insulin release (White et al., 2021). These interactions highlight the need for careful monitoring of caffeine intake in T2DM patients undergoing pharmacological treatment.
Conversely, decaffeinated coffee appears to exert more favourableeffects on blood glucose regulation in T2DM patients. This is largely due to its bioactive compounds, particularly polyphenols and chlorogenic acids, which have demonstrated potential in improving insulin sensitivity and reducing oxidative stress (Salazar-Martinez et al., 2023). Unlike caffeine, decaffeinated coffee does not stimulate catecholamine release or interfere with adenosine receptor function, making it a safer option for individuals managing diabetes (van Dam et al., 2020). In a randomized controlled trial conducted by Greenberg et al. (2022), T2DM patients who consumed decaffeinated coffee for 12 weeks exhibited improved fasting blood glucose levels and enhanced insulin sensitivity compared to those consuming caffeinated coffee. These findings suggest that the polyphenol content of decaffeinated coffee may complement the action of antidiabetic medications rather than opposing their effects. Moreover, decaffeinated coffee has been shown to reduce markers of inflammation and oxidative stress, which are commonly elevated in T2DM patients and can exacerbate insulin resistance (Freeman et al., 2020). Another important consideration is the long-term consumption of caffeine versus decaffeinated coffee in the context of glycemic control. While acute caffeine intake has been consistently associated with impaired insulin sensitivity, some longitudinal studies suggest that habitual caffeine consumption may lead to adaptive metabolic changes that partially counteract these effects (Lopez-Garcia et al., 2019). However, such adaptations vary between individuals and may not be sufficient to neutralize the negative impact of caffeine on medication efficacy (Minges et al., 2021). In contrast, regular consumption of decaffeinated coffee has been linked to sustained improvements in glucose metabolism without causing the insulin resistance associated with caffeine (Salazar-Martinez et al., 2023). This distinction is crucial for T2DM patients, as even minor fluctuations in blood glucose levels can increase the risk of complications such as cardiovascular disease and neuropathy (White et al., 2021). In conclusion, caffeine can significantly affect blood glucose regulation in T2DM patients, primarily by impairing insulin sensitivity and interfering with the action of key antidiabetic medications (Robinson et al., 2022). These effects are mediated through adenosine receptor antagonism, catecholamine release, and enhanced hepatic glucose output. Decaffeinated coffee, on the other hand, appears to offer metabolic benefits through its polyphenol content, improving insulin sensitivity and reducing oxidative stress without the adverse effects associated with caffeine (Greenberg et al., 2022). Given the potential for caffeine to undermine glycemic control and the positive effects of decaffeinated coffee, it is advisable for T2DM patients to monitor their coffee consumption carefully, particularly when using pharmacological treatments for blood glucose management (van Dam et al., 2020).
Clinical Implications and Future Directions
Understanding the effects of caffeine and decaffeinated coffee on blood glucose regulation carries significant clinical implications for both healthy individuals and patients with type 2 diabetes mellitus (T2DM) on antidiabetic medications. For T2DM patients, managing blood glucose levels is crucial to prevent complications such as cardiovascular disease, neuropathy, and nephropathy. Evidence suggests that caffeine consumption may disrupt glycemic control by impairing insulin sensitivity and interfering with the efficacy of common antidiabetic medications (Greenberg et al., 2022). This disruption is particularly concerning for patients using insulin or insulin-sensitizing drugs like metformin, as caffeine-induced hyperglycemia can reduce the therapeutic effectiveness of these medications (White et al., 2021). Consequently, healthcare professionals should consider caffeine intake when designing individualized treatment plans for T2DM patients to ensure optimal blood glucose control. Limiting caffeine consumption or transitioning to decaffeinated coffee may mitigate these adverse effects while preserving the benefits of bioactive compounds present in coffee (Salazar-Martinez et al., 2023). For healthy individuals, the clinical implications of caffeine on glucose metabolism are less pronounced but still noteworthy. While acute caffeine intake may lead to temporary elevations in blood glucose levels, long-term consumption is associated with a reduced risk of developing T2DM (Lopez-Garcia et al., 2019). This paradox suggests that chronic caffeine consumption may induce adaptive metabolic changes that counteract its immediate glucose-raising effects. However, these adaptations are influenced by genetic variations in caffeine metabolism, meaning that not all individuals experience the same protective benefits (Freeman et al., 2020). Decaffeinated coffee, on the other hand, consistently demonstrates positive effects on glucose metabolism without the risk of impaired insulin sensitivity. As such, promoting decaffeinated coffee consumption may be a safer and more effective strategy for individuals at risk of developing T2DM, particularly those with prediabetes or metabolic syndrome (van Dam et al., 2020). Future research should focus on elucidating the long-term metabolic effects of caffeine and decaffeinated coffee, particularly in diverse patient populations with varying genetic backgrounds. Large-scale, randomized controlled trials are needed to assess the impact of chronic caffeine consumption on blood glucose regulation and its interaction with different classes of antidiabetic medications (Robinson et al., 2022). Additionally, exploring the specific mechanisms through which bioactive compounds in decaffeinated coffee improve insulin sensitivity could inform the development of novel therapeutic strategies for managing T2DM (Minges et al., 2021). Personalized medicine approaches, which consider individual variations in caffeine metabolism and drug response, may offer more tailored recommendations for coffee consumption in patients with metabolic disorders (White et al., 2021). Another promising avenue for future research involves investigating the combined effects of caffeine and other dietary factors on glucose metabolism. For instance, the timing of caffeine intake relative to meals and medication administration may influence its impact on blood glucose levels (Gonçalves et al., 2017). Understanding these interactions could lead to more precise dietary guidelines for T2DM patients to minimize caffeine’s adverse effects while maintaining glycemic control. Moreover, longitudinal studies examining the effects of decaffeinated coffee on inflammatory markers and oxidative stress may further clarify its role in reducing the risk of diabetes-related complications (Greenberg et al., 2022). In clinical practice, healthcare providers should advise T2DM patients to monitor their caffeine intake carefully and consider switching to decaffeinated alternatives when appropriate. Patient education regarding the potential metabolic effects of caffeine and the benefits of decaffeinated coffee is essential for improving treatment adherence and achieving better glycemic outcomes (Salazar-Martinez et al., 2023). By incorporating evidence-based recommendations on coffee consumption into clinical guidelines, healthcare professionals can support more comprehensive and individualized approaches to diabetes management. Ultimately, continued research and clinical awareness are crucial for optimizing patient outcomes and addressing the complex relationship between caffeine, decaffeinated coffee, and blood glucose regulation (Lopez-Garcia et al., 2019).
REFERENCES
Archana D., K. Karthickeyan*, Impact of Caffeine and Decaffeinated Coffee on Blood Glucose Levels in Healthy Individuals and Type 2 Diabetes Patients on Antidiabetic Medications, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 6, 2073-2083. https://doi.org/10.5281/zenodo.15638422
10.5281/zenodo.15638422
