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Show references American Diabetes Association. Standards of medical care in diabetes — Diabetes Care. Dungan K, et al. Glucagon-like peptide 1 receptor agonists for the treatment of type 2 diabetes mellitus. Accessed April 10, Goldman L, et al. Diabetes mellitus. In: Goldman-Cecil Medicine. Elsevier; Accessed April 11, Hu M, et al.
Effect of hemoglobin A1c reduction or weight reduction on blood pressure in glucagon-like peptide-1receptor agonist and sodium-glucose cotransporter-2 inhibitor treatment in type 2 diabetes mellitus: A meta-analysis.
Journal of the American Heart Association. Boyle JG, et al. Cardiovascular benefits of GLP-1 agonists in type 2 diabetes: A comparative review. Clinical Science. Bellastella G, et al. Glucagon-like peptide-1 receptor agonists and prevention of stroke systematic review of cardiovascular outcome trials with meta-analysis.
Perreault L. Obesity in adults: Drug therapy. Accessed May 13, Products and Services Assortment of Health Products from Mayo Clinic Store A Book: The Essential Diabetes Book.
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Research Faculty. International Patients. Financial Services. Community Health Needs Assessment. The use of intensive insulin therapy may lead to partial recovery of beta cell function when used in people with metabolic decompensation, and studies suggest that early insulin treatment may induce remission in people with newly diagnosed type 2 diabetes 28,29— Trials of this approach are ongoing.
The natural history of type 2 diabetes is that of ongoing beta cell function decline, so blood glucose BG levels often increase over time even with excellent adherence to healthy behaviours and therapeutic regimens Treatment must be responsive as therapeutic requirements may increase with longer duration of disease.
If A1C target is not achieved or maintained with current pharmacotherapy, treatment intensification is often required. A review of potential precipitants of increasing A1C e.
infection, ischemia and medication adherence should first be conducted, and current therapy may need to be modified if there are significant barriers to adherence. Healthy behaviour interventions, including nutritional therapy and physical activity, should continue to be optimized while pharmacotherapy is being intensified.
Metformin should be continued with other agents unless contraindicated. In general, when combining antihyperglycemic agents with or without insulin, classes of agents that have different mechanisms of action should be used. sulfonylureas and meglitinides or DPP-4 inhibitors and GLP-1 receptor agonists is currently untested, may be less effective at improving glycemia and is not recommended at this time.
Table 1 identifies the mechanism of action for all classes of antihyperglycemic agents to aid the reader in avoiding the selection of agents with overlapping mechanisms. A1C , glycated hemoglobin; CHF , congestive heart failure; CV , cardiovascular; CVD , cardiovascular disease; DKA , diabetic ketoacidosis; eGFR , estimated glomerular filtration rate; HHS , hyperosmolar hyperglycemic state.
Figure 1 continued Management of hyperglycemia in type 2 diabetes. In deciding upon which agent to add after metformin, there must be consideration of both short-term effects on glycemic control and long-term effects on clinical complications.
While intensive glycemic control with a variety of agents is associated with a reduction in microvascular complications 3 and possibly CV complications 34 see Targets for Glycemic Control chapter, p.
S42 , Table 1 highlights agent-specific effects on CV or microvascular complications e. CKD based on trials where glycemic differences between treatment arms were minimized. The effect of exogenous insulin on the risk of CV complications has been shown to be neutral 35, There was a neutral effect on CV outcomes and cancer, and a slight increase in hypoglycemia and weight 36, Earlier trials evaluated effects of thiazolidinediones on CV events.
Meta-analyses of smaller studies suggested possible higher risk of myocardial infarction MI with rosiglitazone 38,39 ; however, CV events were not significantly increased in a larger randomized clinical trial 40, Conversely, the evidence for pioglitazone suggests a possible reduced risk of CV events, but the primary CV outcome was neutral 42, While these agents have comparable glucose-lowering effects to other drugs, the edema, weight gain, risk of congestive heart failure CHF 44 , increased risk of fractures 45,46 and inconsistent data regarding MI risk with rosiglitazone 38—40 and bladder cancer risk with pioglitazone significantly limit the clinical utility of this drug class 47, Based on controversies regarding rosiglitazone, in , the United States Food and Drug Administration FDA required that all new antidiabetic therapies undergo evaluation for CV safety at the time of approval.
Subsequently, several industry-sponsored placebo-controlled trials were initiated to evaluate CV outcomes of drugs from 3 newer classes: DPP-4 inhibitors, GLP-1 receptor agonists and SGLT2 inhibitors see Table 2. Trial durations are from 1. Therefore, findings from these trials are directly relevant to people with established type 2 diabetes and clinical CV disease or multiple risk factors.
Studies have not evaluated whether findings are generalizable to people with new-onset type 2 diabetes or those at average or lower CV risk. Three DPP-4 inhibitor trials have been completed Table 2. None have shown inferiority or superiority compared to placebo for the risk of major CV events 49, There was a non-statistically significant increase in hospitalizations for CHF with alogliptin in the Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care EXAMINE trial 49 and there is limited experience treating people with a history of CHF with linagliptin; therefore, these agents should be used with caution in that setting.
Moreover, a secondary analysis of the data suggested a possibly higher relative risk of unstable angina and all-cause mortality with saxagliptin in those under 65 years The significance of these findings is unclear and further studies are needed.
The GLP-1 receptor agonist, lixisenatide, was also shown to be non-inferior to placebo after a median 2. Figure 2 Antihyperglycemic medications and renal function. Based on product monograph precautions. CKD, chronic kidney disease; CV , cardiovascular; GFR , glomerular filtration rate; TZD , thiazolidinedione.
Three approved and one unapproved antihyperglycemic agent, thus far, have shown benefit in reducing major CV outcomes in individuals with clinical CVD, the SGLT2 inhibitors empagliflozin 53 and canagliflozin 54 , and the GLP-1 receptor agonists liraglutide 55 and semaglutide Those treated with empagliflozin had significantly fewer CV events CV death, nonfatal MI, nonfatal stroke compared to placebo-treated participants after a median 3.
In a secondary analysis, empagliflozin was associated with a significant reduction in hospitalizations for CHF 4. Recent meta-analyses of SGLT2 inhibitors confirmed a significant benefit of this class of agents on major CV outcomes, which was largely driven by EMPA-REG OUTCOME results 58— The CANagliflozin cardioVascular Assessment Study CANVAS program, which integrated findings from 2 placebo-controlled trials CANVAS and CANVAS-R , evaluated the CV effects of canagliflozin The trials enrolled 10, participants 4, in CANVAS and 5, in CANVAS-R with type 2 diabetes mean duration Over a median follow up of 2.
There were no statistical differences in the individual components of the composite outcome. There was a reduction in hospitalization for heart failure and in several adverse renal outcomes; however, these were considered exploratory outcomes due to pre-specified rules of evidence hierarchy.
While one-third of participants did not have CVD, a significant decrease in the primary endpoint was only found in those with CVD. Therefore, as with other CV outcome trials, these results largely apply to people with type 2 diabetes requiring add-on antihyperglycemic therapy who have established clinical CVD.
Canagliflozin was also associated with an increase in fracture rates HR 1. Importantly, canagliflozin was associated with doubling in the risk of lower extremity amputation HR 1. This risk was strongest in participants with a prior amputation. Canagliflozin should, therefore, be avoided in people with a prior amputation, as the harms appear to be greater than the benefits in that population.
The Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results LEADER trial enrolled 9, participants with longstanding type 2 diabetes median duration Over a median follow up of 3. Therefore results are most applicable to people with type 2 diabetes with clinical CVD requiring add-on antihyperglycemic therapy.
The Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes SUSTAIN-6 enrolled 3, participants with a mean duration of type 2 diabetes of After a median follow up of 2. There was, however, a higher rate of diabetic retinopathy complications in the semaglutide group compared to placebo group 3.
It is unclear at this time if there is a direct effect of semaglutide or other explanations for this unexpected difference in retinopathy complication rates, although the risk appeared greatest in individuals with pre-existing retinopathy and rapid lowering of A1C.
All 4 trials reported lower rates of kidney disease progression in the treated groups compared to placebo 53,55, It should also be noted that the majority of people in these trials had pre-existing CVD and required add-on antihyperglycemic therapy.
In addition, because these were placebo-controlled trials, no conclusions can be made about how the cardioprotective properties of empagliflozin, canagliflozin, liraglutide and semaglutide compare to those of other agents. CV outcome trials for other agents are expected to be completed by ; therefore, based on evidence to date, a GLP-1 receptor agonist or SGLT2 inhibitor with demonstrated CV outcome benefit should be considered as initial add-on therapy for people with pre-existing type 2 diabetes and clinical CV disease who have not achieved target A1C on existing treatment to reduce CV risk.
A careful review of the methods and findings from these trials was conducted by an independent committee. While primary analyses results were similar for canagliflozin, empagliflozin and liraglutide, it was concluded that the strength of evidence for CV benefit was weaker for canagliflozin than for the other agents.
This conclusion was based on three factors. First, in an interim analysis of the CANVAS study for medication approval necessitated unblinding of study data. A decision was then made to combine this study with the CANVAS-R study, presumably to provide greater power for CV outcomes.
The interim unblinding and protocol revision were viewed as potential threats to internal validity, thereby weakening the strength of evidence for benefit. Second, while canagliflozin was associated with a significant decrease in the composite MACE outcome, there was no significant benefit on individual outcomes, such as all-cause or CV mortality.
Third, the findings of increased risk of fractures and amputations with canagliflozin treatment in the context of a noninferiority design where the comparator is placebo was particularly concerning, indicating that harms may outweigh benefits.
For these reasons, the committee decided that the uncertainty regarding benefits should be acknowledged with a lower grade of recommendation for canagliflozin than for other agents with demonstrated CV benefit.
In the absence of evidence for long-term clinical benefit, agents effective at A1C lowering should be considered in terms of both the degree of baseline hyperglycemia needing correction, and any heightened concerns regarding hypoglycemia e.
elderly people or those with renal or hepatic dysfunction see Diabetes in Older People chapter, p. While most medications added to metformin lower A1C to a similar extent, insulin and insulin secretagogues are associated with higher rates of hypoglycemia than other agents 21,23,24, In those who are stable, other agent-specific advantages and disadvantages should be weighed as treatment is individualized to best suit the patient's needs and preferences.
Each of the agents listed in Table 1 and Figure 1 has advantages and disadvantages to consider. Figure 2 illustrates the basis on which agent selection is influenced by renal function as dictated by product monograph precautions.
Recent meta-analyses have summarized head-to-head comparisons of metformin-based combinations 19,24,62, Combinations of metformin with a sulfonylurea, a thiazolidinedione TZD , an SGLT2 inhibitor and a DPP-4 inhibitor have comparable A1C-lowering effects 19,24,62—66 , while the combination of metformin with a GLP-1 receptor agonist reduced A1C more than combination with a DPP-4 inhibitor.
TZDs, insulin and sulfonylureas are associated with the most weight gain 1. Hypoglycemia risk is also lower with TZDs, DPP-4 inhibitors, SGLT2 inhibitors and GLP-1 receptor agonists compared to sulfonylureas and insulin 19,24,62—65,67, Network meta-analyses that indirectly compared the net benefits of second- and third-line treatment options have found similar results 21,23,24,69— Evidence on comparative effectiveness of acarbose and orlistat is limited, although they are associated with a low risk of hypoglycemia and weight gain.
The safety of incretin agents, SGLT2 inhibitors and TZDs in pregnancy is unknown; therefore, these agents should be avoided or discontinued in women who are pregnant or planning a pregnancy see Diabetes and Pregnancy chapter, p.
If a sulfonylurea is added to metformin, gliclazide should be considered as first choice as it is associated with a lower risk of hypoglycemia 67,72 , CV events and mortality relative to other sulfonylureas Glimepiride is also associated with a lower risk of CV events and mortality 73 , but has a similar rate of hypoglycemia 67,72 compared to other sulfonylureas.
For people already taking metformin and a sulfonylurea, the addition of either a DPP-4 inhibitor, a GLP-1 receptor agonist or SGLT2 inhibitor may be considered as they are associated with effective A1C lowering with less hypoglycemia than insulin or TZDs 21,69,70,74,75 ; GLP-1 receptor agonists and SGLT2 inhibitors are also associated with weight loss 70,71 see Weight Management in Diabetes chapter, p.
For instance, the combination of a DPP-4 inhibitor or a GLP-1 receptor agonist and an SGLT2 inhibitor added to metformin has been shown to be as safe and more efficacious at lowering A1C after 24 weeks than either agent alone 76, SGLT2 inhibitors and GLP-1 receptor agonists added to metformin have also been shown to reduce systolic BP compared to metformin alone, and add-on of SGLT2 inhibitors reduce systolic BP more than add-on of sulfonylureas or DPP-4 inhibitors A combination of noninsulin antihyperglycemic agents and insulin often effectively controls glucose levels.
Insulin treatment includes long-acting or intermediate-acting insulin analogue injections once or twice daily for basal glycemic control, and bolus injections at mealtimes for prandial glycemic control. Adding insulin to noninsulin antihyperglycemic agent s may result in better glycemic control with a smaller dose of insulin 78 , and may induce less weight gain and less hypoglycemia than that seen when non-insulin antihyperglycemic agents are stopped and insulin is used alone 79, A single injection of an intermediate-acting NPH 81 or long-acting insulin analogue insulin glargine U, insulin glargine U, insulin detemir or insulin degludec 82—84 may be added.
The addition of bedtime insulin to metformin therapy leads to less weight gain than insulin plus a sulfonylurea or twice-daily NPH insulin When insulin is used in type 2 diabetes, the insulin regimen should be tailored to achieve good metabolic control while trying to avoid hypoglycemia.
With intensive glycemic control, there is an increased risk of hypoglycemia, but this risk is lower in people with type 2 diabetes than in those with type 1 diabetes. The mode of insulin administration continuous subcutaneous infusion vs. injections , the number of insulin injections 1 to 4 per day and the timing of injections may vary depending on each individual's situation As type 2 diabetes progresses, insulin requirements will likely increase and higher doses of basal insulin intermediate-acting or long-acting analogues may be needed.
DPP-4 inhibitors, GLP-1 receptor agonists and SGLT2 inhibitors have been shown to be efficacious at further lowering glucose levels when combined with insulin therapy 87— A meta-analysis determined that the addition of a GLP-1 receptor agonist to basal insulin regimens results in greater A1C reduction, more weight loss and less hypoglycemia compared to the addition of bolus insulin A GLP-1 receptor agonist should, therefore, be considered before bolus insulin as add-on therapy in people on basal insulin with or without other agents who require antihyperglycemic treatment intensification if there are not barriers to affordability or access.
If glycemic control is suboptimal on treatment regimens that include basal insulin with other agents, bolus insulin at mealtimes short- or rapid-acting analogues may be added. Generally, once bolus insulin is introduced into a treatment regimen, either as a separate mealtime bolus or as part of a premixed containing regimen, insulin secretagogues, such as sulfonylureas and meglitinides, should be discontinued.
Concomitant therapy with metformin and, if applicable, a GLP-1 receptor agonist, DPP-4 inhibitor or SGLT2 inhibitor should be continued with regimens containing bolus insulin unless contraindicated, to allow for improved glycemic control with less risk of weight gain and hypoglycemia The reduction in A1C achieved with insulin therapy depends on the dose and number of injections per day A meta-analysis of 12 articles compared basal-bolus and biphasic insulin regimens, and found that both approaches are equally efficacious at lowering A1C, with comparable effects on hypoglycemia risk and weight—although basal-bolus regimens were modestly more efficacious in people with type 2 diabetes already on insulin Bolus insulin should be initiated using a stepwise approach starting with 1 injection at the largest meal and additional mealtime injections at 3-month intervals if needed , as it was shown to be as efficacious at A1C lowering as a full basal-bolus regimen, and is associated with less hypoglycemia and greater patient satisfaction after 1 year Lower rates of hypoglycemia have been observed in some studies of individuals with type 2 diabetes treated with rapid-acting insulin analogues insulin aspart, insulin lispro, insulin glulisine compared to those treated with short-acting regular insulin — Use of long-acting basal insulin analogues insulin detemir, insulin glargine, insulin degludec in those already on antihyperglycemic agents reduces the relative risk of symptomatic and nocturnal hypoglycemia compared to treatment with NPH insulin 83,,— Meta-analyses indicate a relative reduction of 0.
NPH Insulin degludec has been associated with lower rates of overall and nocturnal hypoglycemia compared to glargine U 82,84, After 32 weeks of treatment, insulin degludec was associated with a significantly lower rate of the primary endpoint of overall symptomatic hypoglycemic episodes rate ratio 0.
The proportions of patients with hypoglycemic episodes were 9. The Trial Comparing Cardiovascular Safety of Insulin Degludec versus Insulin Glargine in Patients with Type 2 Diabetes at High Risk of Cardiovascular Events DEVOTE randomized patients with type 2 diabetes at high risk of CV disease to insulin degludec or glargine U, and found no difference in the primary outcome of CV events but a significant decrease in severe hypoglycemia with degludec 4.
There is also some evidence of lower hypoglycemia rates with glargine U compared to glargine U and may also be considered over glargine U if reducing hypoglycemia is a priority Efficacy and rates of hypoglycemia are similar between glargine U and detemir Aside from effects of some antihyperglycemic agents on the occurrence of hypoglycemia and weight, there are adverse effects unique to each agent Table 1.
Gastrointestinal side effects are more common with metformin, alpha glucosidase inhibitors, GLP-1 receptor agonists and orlistat than with other agents.
Metformin can cause diarrhea, which tends to resolve over time and is minimized with starting at a low dose and subsequent slow titration of the dosage.
Extended-release metformin can also be used to improve tolerability in individuals experiencing gastrointestinal side effects with immediate-release metformin — Metformin is also associated with an approximate 2-fold increased incidence of vitamin B12 deficiency — , and vitamin B12 levels should be measured periodically in people taking metformin or with signs or symptoms of deficiency such as impaired proprioception or peripheral neuropathy.
GLP-1 receptor agonists and, less commonly, DPP-4 inhibitors can cause nausea and GLP-1 receptor agonists can also cause diarrhea.
A meta-analysis comparing the risk of congestive heart failure between antihyperglycemic therapies found an increased risk with TZDs and DPP-4 inhibitors driven by higher risk with saxagliptin 44 , although another meta-analysis and a large observational study of over one million participants failed to find an increased risk of heart failure with DPP-4 inhibitors compared to other agents.
Reports of acute pancreatitis have been noted with DPP-4 inhibitors and GLP-1 receptor agonists. A small significant increase in pancreatitis but not pancreatic cancer was seen with DPP4-inhibitors in a meta-analysis of 3 large randomized controlled trials of over 20, participants However, a recent large Canadian observational study of over 1.
SGLT2 inhibitors are associated with a 3- to 4-fold increased risk of genital mycotic infections 19,69,95 , as well as higher rates of urinary tract infections, volume depletion, rare acute kidney injury and rare DKA , Canagliflozin treatment is associated with an increased risk of fractures 54, and a twofold increased risk of amputations In a retrospective analysis, empagliflozin was not associated with an increased risk of amputations in the EMPA-REG trial There is evidence of a higher risk of bladder cancer with pioglitazone in some studies 47,48 but not others — , and some reports of increased bladder cancer risk with dapagliflozin GLP-1 receptor agonists have been shown to promote the development of pancreatic and medullary thyroid cancer in rodents, but an increased risk has not been seen in humans Semaglutide was associated with a higher risk of retinopathy in SUSTAIN-6 see above Earlier epidemiological evidence suggesting a possible link between insulin glargine and cancer has not been substantiated in review of clinical trial data for either glargine or detemir 36,, Insulin glargine U may be considered over insulin glargine U to reduce overall and nocturnal hypoglycemia [Grade C, Level 3 ].
A1C , glycated hemoglobin; BG , blood glucose; BP , blood pressure; CHF , congestive heart failure; CHD , coronary heart disease; CI , confidence interval; CV , cardiovascular; CVD , cardiovascular disease; DKA , diabetic ketoacidosis; HR , hazard ratio; MI ; myocardial infarct; NPH , neutral protamine Hagedorn; TZD , thiazolidinedione.
Appendix 9. Examples of Insulin Initiation and Titration Regimens in People With Type 2 Diabetes. Literature Review Flow Diagram for Chapter Pharmacologic Glycemic Management of Type 2 Diabetes in Adults.
From: Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group P referred R eporting I tems for S ystematic Reviews and M eta- A nalyses: The PRISMA Statement. PLoS Med 6 6 : e pmed For more information, visit www.
Goldenberg reports personal fees from Abbott, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, Novo Nordisk, Sanofi, and Servier, outside the submitted work. MacCallum reports personal fees from Janssen and Novo Nordisk, outside the submitted work.
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Next Previous. Key Messages Recommendations Figures Full Text References. Chapter Headings Introduction Treatment Regimens Effects of Antihyperglycemic Agents on Microvascular and Cardiovascular Complications Effects of Antihyperglycemic Agents on Glycemic Control and Other Short-Term Outcomes Insulin Treatment in Type 2 Diabetes Adverse Effects Other Relevant Guidelines Relevant Appendices Author Disclosures.
Key Messages Healthy behaviour interventions should be initiated in people newly diagnosed with type 2 diabetes. In the absence of metabolic decompensation, metformin should be the initial agent of choice in people with newly diagnosed type 2 diabetes, unless contraindicated.
In people with clinical cardiovascular CV disease in whom A1C targets are not achieved with existing pharmacotherapy, an antihyperglycemic agent with demonstrated CV outcome benefit should be added to antihyperglycemic therapy to reduce CV risk.
In people receiving an antihyperglycemic regimen containing insulin, in whom glycemic targets are not achieved, the addition of a GLP-1 receptor agonist, DPP-4 inhibitor or SGLT2 inhibitor may be considered before adding or intensifying prandial insulin therapy to improve glycemic control with less weight gain and comparable or lower hypoglycemia risk.
Key Messages for People with Diabetes Some people who have type 2 diabetes can achieve their target blood glucose levels with nutrition guidance and physical activity alone, but most also need glucose-lowering medications.
The decision about which medications are best for you depends on many factors, including your blood glucose level, symptoms, other health problems you have and affordability of medications. Your health-care provider may even combine medications that act differently on your body to help you control your blood glucose.
Glucose-lowering medications for type 2 diabetes include: First-line glucose-lowering medication: Metformin: Metformin is generally the first choice for people with type 2 diabetes because of its safety, low cost and possible heart benefits.
It works by making your body respond better to insulin so that your body uses insulin more effectively. Metformin also lowers glucose production from the liver.
Nausea and diarrhea are possible side effects and usually go away within 1 to 2 weeks as your body gets used to the medicine.
It is associated with a low risk of hypoglycemia and does not cause weight gain. If metformin and healthy behaviour changes are not enough to control your blood glucose level, other medications can be added. Second-line glucose-lowering medication: DPP-4 inhibitors: These medications work to lower blood glucose by increasing insulin levels after meals and lowering glucagon levels a hormone that raises blood glucose.
They do not cause weight gain and are associated with a low risk of hypoglycemia. GLP-1 receptor agonists: These injectable medications act when blood glucose increases after eating. They increase insulin levels, which helps lower blood glucose and lower glucagon levels a hormone that raises blood glucose.
They also slow digestion and reduce appetite. Possible side effects include nausea, which usually goes away with time. They are associated with weight loss and a low risk of hypoglycemia. SGLT2 inhibitors: These medications work by eliminating glucose into the urine. Side effects may include genital yeast infections, urinary tract infections, increased urination and low blood pressure.
Insulin secretagogues meglitinides, sulfonylureas : These medications help your pancreas release more insulin. Possible side effects include hypoglycemia and weight gain. Thiazolidinediones: Like metformin, these medications make the body's tissues more sensitive to insulin.
Side effects include weight gain and an increased risk of heart failure and fractures. Insulin therapy: Some people who have type 2 diabetes need insulin therapy as well. Depending on your needs, your health-care provider may prescribe a mixture of insulin types to use throughout the day and night.
Often, people with type 2 diabetes start insulin use with 1 injection of long-acting insulin at night. Discuss the pros and cons of different treatment plans with your healthcare provider.
Together, you can decide which medication is best for you after considering many factors, including costs and other aspects of your health.
Introduction People with type 2 diabetes form a heterogeneous group. Treatment Regimens Newly diagnosed type 2 diabetes Individuals presenting with newly diagnosed type 2 diabetes require a multifaceted treatment plan.
Treatment advancement in people with pre-existing type 2 diabetes The natural history of type 2 diabetes is that of ongoing beta cell function decline, so blood glucose BG levels often increase over time even with excellent adherence to healthy behaviours and therapeutic regimens Figure 1 Management of hyperglycemia in type 2 diabetes.
Effects of Antihyperglycemic Agents on Microvascular and Cardiovascular Complications In deciding upon which agent to add after metformin, there must be consideration of both short-term effects on glycemic control and long-term effects on clinical complications. Effects of Antihyperglycemic Agents on Glycemic Control and Other Short-Term Outcomes In the absence of evidence for long-term clinical benefit, agents effective at A1C lowering should be considered in terms of both the degree of baseline hyperglycemia needing correction, and any heightened concerns regarding hypoglycemia e.
Insulin Treatment in Type 2 Diabetes A combination of noninsulin antihyperglycemic agents and insulin often effectively controls glucose levels.
Adverse Effects Aside from effects of some antihyperglycemic agents on the occurrence of hypoglycemia and weight, there are adverse effects unique to each agent Table 1. Recommendations Treatment of Newly Diagnosed People with Type 2 Diabetes Healthy behaviour interventions should be initiated at diagnosis [Grade B, Level 2 2 ].
Metformin may be used at the time of diagnosis, in conjunction with healthy behaviour interventions [Grade D, Consensus]. If glycemic targets are not achieved using healthy behaviour interventions alone within 3 months, antihyperglycemic therapy should be added to reduce the risk of microvascular complications [Grade A, Level 1A 3 ].
Metformin should be chosen over other agents due to its low risk of hypoglycemia and weight gain [Grade A, Level 1A 19 ], and long-term experience [Grade D, Consensus]. Individuals with metabolic decompensation e.
marked hyperglycemia, ketosis or unintentional weight loss should receive insulin with or without metformin to correct the relative insulin deficiency [Grade D, Consensus].
The choice should be individualized taking into account the information in Figure 1 and Table 1 [Grade B, Level 2 19 ]. For adults with type 2 diabetes with metabolic decompensation e.
marked hyperglycemia, ketosis or unintentional weight loss , insulin should be used [Grade D, Consensus]. Insulin may be used at any time in the course of type 2 diabetes [Grade D, Consensus] see Appendix 9.
Examples of Insulin Initiation and Titration in People with Type 2 Diabetes. A GLP-1 receptor agonist should be considered as add-on therapy [Grade A, Level 1A 87,97 ], before initiating bolus insulin or intensifying insulin to improve glycemic control with weight loss and a lower hypoglycemia risk compared to single or multiple bolus insulin injections [Grade A, Level 1A 25,98,99 ].
An SGLT2 inhibitor should be considered as add-on therapy to improve glycemic control with weight loss and lower hypoglycemic risk compared to additional insulin [Grade A, Level 1A 27,93,94 ]. A DPP-4 inhibitor may be considered as add-on therapy to improve glycemic control without weight gain or increased hypoglycemia risk compared to additional insulin [Grade B, Level 2 27,91 ].
When bolus insulin is added to antihyperglycemic agents, rapid-acting analogues may be used instead of short-acting regular insulin to improve glycemic control [Grade B, Level 2 ]. Bolus insulin may be initiated using a stepwise approach starting with 1 injection at 1 meal and additional mealtime injections as needed to achieve similar A1C reduction with lower hypoglycemia risk compared to initiating a full basal-bolus injection regimen [Grade B, Level 2 ].
All individuals with type 2 diabetes currently using or starting therapy with insulin or insulin secretagogues should be counselled about the prevention, recognition and treatment of hypoglycemia [Grade D, Consensus].
Metformin, insulin secretagogues and SGLT2 inhibitors should be temporarily withheld during acute illnesses associated with reduced oral intake or dehydration [Grade D, Consensus].
See Appendix 8. Sick Day Medication List. SGLT2 inhibitors should be temporarily withheld prior to major surgical procedures, and during acute infections and serious illness to reduce the risk of ketoacidosis [Grade D, Consensus]. Abbreviations A1C , glycated hemoglobin; BG , blood glucose; BP , blood pressure; CHF , congestive heart failure; CHD , coronary heart disease; CI , confidence interval; CV , cardiovascular; CVD , cardiovascular disease; DKA , diabetic ketoacidosis; HR , hazard ratio; MI ; myocardial infarct; NPH , neutral protamine Hagedorn; TZD , thiazolidinedione.
Other Relevant Guidelines Chapter 8. Targets for Glycemic Control Chapter Glycemic Management in Adults With Type 1 Diabetes Chapter Hypoglycemia Chapter Weight Management in Diabetes Chapter Type 2 Diabetes in Children and Adolescents Chapter Diabetes and Pregnancy Chapter Diabetes in Older People.
Relevant Appendices Appendix 6. Types of Insulin Appendix 7. Therapeutic Considerations for Renal Impairment Appendix 8. Sick-Day Medication List Appendix 9. Author Disclosures Dr. References Gaede P, Lund-Andersen H, Parving HH, et al.
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Please read the Disclaimer at medicayion end of medicatoon Boost endurance snacks. Allergy-friendly snacks 2 diabetes mellitus is Mevication disorder that is known for disrupting the way your body uses glucose Smart insulin delivery ; it also causes other problems with the way diabeyes body stores and processes Smart insulin delivery forms of energy, including fat. All the cells in your body need sugar to work normally. Sugar gets into the cells with the help of a hormone called insulin. In type 2 diabetes, the body stops responding to normal or even high levels of insulin, and over time, the pancreas an organ in the abdomen does not make enough insulin to keep up with what the body needs. Being overweight, especially having extra fat stored in the liver and abdomen, even if weight is normal, increases the body's demand for insulin.
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