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Alternative medicine or supplements for type 2 diabetes treatmentDiabetes and alternative treatment approaches -
A number of immune modulators have been studied in an attempt to prevent or arrest beta cell decline in type 1 diabetes, most with limited success. A few NHP have also been studied in this regard. A randomized controlled trial of people with new-onset type 1 diabetes assessed the effect of vitamin D supplementation on regulatory T Treg cells After 12 months, Treg suppressive capacity was improved, although there was no significant reduction in C-peptide decline.
Observational studies have suggested an inverse relationship between vitamin D levels and the development of type 2 diabetes 13 , although randomized controlled trials are lacking In the large, prospective cohort study, The Environmental Determinants of Diabetes in the Young TEDDY , early probiotic supplementation may reduce the risk of islet autoimmunity in children at the highest genetic risk of type 1 diabetes A number of NHP have been evaluated to assess their effect on the progression from impaired glucose tolerance IGT to diabetes.
Tianqi is a traditional Chinese medicine consisting of 10 different herbs. A systematic review and meta-analysis of observational studies of omega-3 fatty acids or fish intake showed that an increased intake of alpha linoleic acid ALA and fatty fish reduced the risk of type 2 diabetes significantly with ALA, only in Asians In a randomized controlled trial, the traditional Chinese medicine Shenzhu Tiaopi granule SZTP significantly reduced the conversion from IGT to type 2 diabetes to 8.
In adults with type 2 diabetes, the following NHP have been shown to lower glycated hemoglobin A1C by at least 0. These products are promising and merit consideration and further research, but, as they are mostly single, small trials or meta-analyses of such, it is premature to recommend their widespread use.
The following NHP either failed to lower A1C by 0. The following NHP have demonstrated conflicting effects on A1C in trials lasting at least 3 months in adults with type 2 diabetes:. A few products, such as chromium, vitamin D and vanadium, have been the subjects of special interest in diabetes.
Chromium is an essential trace element involved in glucose and lipid metabolism. Early studies revealed that chromium deficiency could lead to IGT, which was reversible with chromium repletion.
This led to a hypothesis that chromium supplementation, in those with both adequate and deficient chromium stores, could lead to improved glucose control in people with diabetes , However, randomized controlled studies of chromium supplementation have had conflicting results, with most showing no benefit on improving A1C — , although some showed an improved fasting glucose level , Most were small studies, of short duration, and some not double-blinded.
More recent meta-analyses have also reported conflicting results, with some concluding no benefit of chromium on reducing A1C, lipids or body weight in people with diabetes , and others reporting some benefit depending upon the dose and formulation consumed The later meta-analysis reported marked heterogeneity and publication bias in the included studies.
Vitamin D has received much interest recently with purported benefits on cardiovascular disease CVD , cancer and diabetes. Randomized controlled trials have not demonstrated a benefit of vitamin D supplementation on glycemic control in diabetes — , further confirmed by meta-analyses , Vanadium, a trace element that is commonly used to treat type 2 diabetes, has not been studied in randomized controlled trials evaluating glycemic control by A1C over a period of 3 months or longer.
A number of NHP have been evaluated for the various co-morbidities and complications of diabetes, including lipids and blood pressure BP in diabetes, as well as CVD, nephropathy, retinopathy and peripheral neuropathy.
As with the studies of glycemic control, most had small sample sizes and meta-analyses had marked heterogeneity of included studies, making strong conclusions difficult. Randomized controlled trials demonstrating a benefit on lipid parameters in diabetes include: Ayurvedic polyherbal formulation 19 , Hintonia latiflora 26 and magnesium In postmenopausal women with type 2 diabetes, vitamin D supplementation for 6 months reduced serum triglycerides TG without effect on other lipid parameters , while a meta-analysis with high heterogeneity showed benefit on lowering total cholesterol and TG Other studies have failed to show significant benefit of vitamin D supplementation on lipids in people with diabetes ,, A meta-analysis of Berberine showed it to reduce TG and increase high-density lipoprotein cholesterol HDL-C more than traditional lipid-lowering drugs, with no difference on total or low-density lipoprotein cholesterol LDL-C Berberine was also shown to reduce total and LDL-C and increase HDL-C combined with traditional lipid-lowering drugs compared with those drugs alone.
Berberine when combined with traditional BP medications can lower systolic BP by an additional 4. In 1 meta-analysis, vitamin D was shown to reduce BP by a statistically significant, but not clinically meaningful amount Ethylene diamine tetra-acetic EDTA acid chelation therapy has been postulated to have a number of cardiovascular CV benefits.
The traditional Chinese medicine product, The Compound Danshen Dripping Pill CDDP , consisting of 3 herbal preparations, was evaluated in a randomized controlled trial of 24 weeks duration, for its effect on the progression of diabetic retinopathy Using a nonstandardized method of grading fluorescence fundal angiography, higher doses of CDDP were found to delay the progression of diabetic retinopathy.
A number of NHP have been reported to improve diabetic nephropathy. Many are of short duration, some without reporting an assessment of renal function or its progression, or with conflicting results on the various measures.
Some products showing a reduction in UAE in people with diabetes include: the traditional Chinese medicines Yiqi Huayu, Yiqi Yangyin , Qidan Dihuang Grain , and Jiangzhuo SKC-YJ , Huangshukuihua Flos Abelmoschi Manihot , , Pueraria lobata gegen, puerarin , Tangshen Formula , Zishentongluo ZSTL 45 , vitamin D , and vitamin D analogue paricalcitol in type 1 diabetes Topical Citrullus colocynthis bitter apple extract oil was studied in a small randomized controlled trial in people with painful diabetic polyneuropathy After 3 months, there was a significantly greater decrease in mean pain score and improvement in nerve conduction velocities compared with placebo.
A meta-analysis of puerarin in diabetic peripheral neuropathy reported benefits in pain scores and NCS In a small randomized controlled trial, the traditional Chinese medicine MHGWT showed reduced pain scores compared with placebo after 12 weeks of treatment A number of the above and other NHP have been evaluated for their effects on various pre-clinical parameters, biomarkers and surrogate clinical markers involved in the pathogenesis of diabetes and its complications.
A discussion of these papers is beyond the scope of this chapter. It is important to consider potential harm from the use of NHP. A number of studies of NHP report adverse events, such as gastrointestinal Fenugreek, Berberine, TM81, bitter melon, oral aloe vera and dizziness JYTK.
In 1 trial of Tinospora crispa, hepatotoxicity was seen in 2 participants Large doses of Citrullus colocyn can induce diarrhea, but no side effects were reported in the lower doses used in 1 trial Momordica charantia, an NHP commonly used for glycemic control, is an abortifacient Most clinical trials have evaluated small sample sizes over relatively short periods of time and, thus, may not identify all potential side effects or risks.
The Xiaoke Pill contains glibenclamide glyburide Nettle has insulin secretagogue, peroxisome proliferator-activated receptor PPAR and alpha-glucosidase activities. Only NHPs that are properly labelled with a valid natural product number NPN should be used to avoid adulteration with unlabelled pharmaceuticals or other contaminants.
Drug-herb interactions may also occur. The most well described is Hypericum perforatum St. John's wort , which can affect the metabolism of many drugs, including statins, by inducing cytochrome P 3A4 CYP3A4. Some studies have reported poorer glycemic control in people using glucosamine sulfate for osteoarthritis, but a systematic review concluded that the evidence does not support this concern A number of complementary and alternative approaches have been studied to some degree for diabetes and its complications, others have not.
Included here are studies of yoga, traditional Chinese medicine and reflexology. Other modalities of CAM, such as chiropractic or osteopathic manipulation, homeopathy, shiatsu, registered massage therapy or craniosacral therapy do not have studies specific to diabetes.
The Sanskrit definition of yoga means union or connection. Yoga is a Hindu spiritual discipline. There are many types of yoga, each with its own techniques and methods to awaken greater awareness and connection to self and life.
Most practices of yoga include a series of physical postures, breathing and meditation for health, relaxation and overall well-being. Yoga or yoga therapy is often included in a holistic practitioner's chiropractor, naturopath, osteopath, shiatsu therapist plan of management for stress reduction and physical strengthening.
Studies of yoga in the management of people with type 2 diabetes show some benefit on glycemic control, lipids and BP, although published studies are generally of short duration with small numbers.
In a systematic review and meta-analysis, yoga was found to have positive effects on reducing A1C, as well as fasting and postprandial glucose values There was high heterogeneity among the studies included in the analysis.
Other systematic reviews and meta-analyses showed similar improvements in glycemic parameters, as well as improvements in the lipid profile and BP, with similar limitations in the individual studies included , see Physical Activity and Diabetes chapter, p.
In a meta-analysis of smaller studies looking at comparing the effectiveness of the leisure activities yoga, walking and tai chi on glycemic control in people with type 2 diabetes, yoga with regular frequency 3 times a week was shown to be more effective than tai chi or walking in lowering A1C levels TCM works within a different paradigm than Western Medicine and, as such, can be difficult to study by Western research techniques.
Treatments are complex and focused on individual imbalances detected by pulse and tongue diagnosis rather than specific diseases.
Most research on the effectiveness of TCM for people with diabetes is based on specific techniques or Chinese herbal remedies as reviewed above. Acupuncture is a branch of TCM involving the stimulation of specific points along energy meridians throughout the body to either sedate or tonify the flow of energy.
There are various techniques of acupuncture, such as electro and laser acupuncture, and different systems of acupuncture, including scalp and auricular acupuncture. The system and technique most commonly referred to and most often studied refers to the technique of penetrating the skin at specific acupuncture points with thin solid metal needles that are manipulated by the hands.
Acupuncture has not been shown to improve A1C in people with diabetes, with 1 small randomized controlled trial showing it to be no different than placebo on FPG and oral glucose tolerance testing OGTT A meta-analysis of acupuncture for diabetic gastroparesis concluded that acupuncture improved some dyspeptic symptoms, such as nausea, vomiting, loss of appetite and stomach fullness, with no improvement in solid gastric emptying A systematic review of randomized controlled trials of manual acupuncture for the treatment of diabetic peripheral neuropathy reported that manual acupuncture had a better effect on global symptom improvement compared with vitamin B12 or no treatment, and that the combination of manual acupuncture and vitamin B12 had a better effect compared with vitamin B12 alone.
However, the authors could not draw clinically relevant conclusions because of high risks of bias in the studies included Tai chi is an ancient mind and body practice involving gentle, slow, continuous body movements with mental focus, breathing and relaxation.
Although there may be some benefit in quality of life, there is little evidence for benefit of tai chi on glycemic control in diabetes , Manual therapies, including chiropractic, physiotherapy, shiatsu, registered massage therapy and craniosacral therapy have no randomized controlled trial data in people with diabetes.
A few small studies on tactile massage, a superficial gentle form of massage, have failed to demonstrate a significant beneficial effect on A1C — Reflexology is a system of massage based on the theory that reflex points on the feet, hands and head are linked to other internal parts of the body.
In a small, open-label, randomized controlled trial in people with diabetic peripheral neuropathy, foot reflexology was shown to reduce A1C and FPG, and improve pain scores and nerve conduction velocity Health-care providers should ask about the use of complementary and alternative medicine in people with diabetes [Grade D, Consensus].
There is insufficient evidence to make a recommendation regarding efficacy and safety of complementary or alternative medicine for individuals with diabetes [Grade D, Consensus]. A1C , glycated hemoglobin; ALA , alpha linoleic acid; BP , blood pressure; CAM , complementary or alternative medicine; CV , cardiovascular; CVD , cardiovascular disease; FPG , fasting plasma glucose; HDL-C , high-density lipoprotein cholesterol; IGT , impaired glucose tolerance; LDL-C , low-density lipoprotein cholesterol; MI , myocardial infarct; NCS , nerve conduction studies; NHP , natural health product; NPN , natural product number; OGTT , oral glucose tolerance test; TCM , traditional Chinese medicine; TG , triglycerides, UAE , urinary albumin excretion.
Literature Review Flow Diagram for Chapter Complementary and Alternative Medicine for Diabetes. 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. Grossman reports grants and personal fees from Novo Nordisk, Janssen, and Eli Lilly; grants from Merck, Takeda, Sanofi, AstraZeneca, and Lexicon, outside the submitted work; and previous employee now retired of Eli Lilly Canada.
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Next Previous. Key Messages Recommendations Figures Full Text References. Chapter Headings Introduction NHP for the Prevention and Treatment of Diabetes and Its Complications NHP for the Prevention and Treatment of Diabetes NHP for the Treatment of the Co-Morbidities and Complications of Diabetes Adverse Effects Other Complementary and Alternative Approaches for the Prevention and Treatment of Diabetes and Its Complications Yoga Traditional Chinese Medicine Manual Therapies Other Relevant Guidelines Author Disclosures.
Key Messages for People with Diabetes Many people with diabetes use complementary medicine along with or alternative medicine instead of with conventional medications for diabetes.
Although some of these therapies may have the potential to be effective, they have not been sufficiently studied and others can be ineffective or even harmful. Introduction Despite advances in the management of type 1 and type 2 diabetes, therapeutic targets are often not met.
NHP for the Prevention and Treatment of Diabetes and Its Complications In Canada, NHP are defined as vitamins and minerals, herbal remedies, homeopathic medicines, traditional medicines, such as traditional Chinese medicines, probiotics, and other products like amino acids and essential fatty acids 8.
NHP for the Prevention and Treatment of Diabetes A number of immune modulators have been studied in an attempt to prevent or arrest beta cell decline in type 1 diabetes, most with limited success. rose hip 61 Salvia officinalis 62 Soy phytoestrogens 63 Tinospora cordifolia 64 Tinospora crispa 65 Vitamin C 66—68 Vitamin E 69—73 The following NHP have demonstrated conflicting effects on A1C in trials lasting at least 3 months in adults with type 2 diabetes: Cinnamon 74—79 Coenzyme Q10 80—83,85,86 Ipomoea batatas caiapo 87,88 L-carnitine 89—92 Magnesium 93—99 Omega 3 fatty acids , Probiotics , Zinc , A few products, such as chromium, vitamin D and vanadium, have been the subjects of special interest in diabetes.
NHP for the Treatment of the Co-Morbidities and Complications of Diabetes A number of NHP have been evaluated for the various co-morbidities and complications of diabetes, including lipids and blood pressure BP in diabetes, as well as CVD, nephropathy, retinopathy and peripheral neuropathy.
Adverse Effects It is important to consider potential harm from the use of NHP. Other Complementary and Alternative Approaches for the Prevention and Treatment of Diabetes and Its Complications A number of complementary and alternative approaches have been studied to some degree for diabetes and its complications, others have not.
Yoga The Sanskrit definition of yoga means union or connection. Recommendations Health-care providers should ask about the use of complementary and alternative medicine in people with diabetes [Grade D, Consensus].
Abbreviations: A1C , glycated hemoglobin; ALA , alpha linoleic acid; BP , blood pressure; CAM , complementary or alternative medicine; CV , cardiovascular; CVD , cardiovascular disease; FPG , fasting plasma glucose; HDL-C , high-density lipoprotein cholesterol; IGT , impaired glucose tolerance; LDL-C , low-density lipoprotein cholesterol; MI , myocardial infarct; NCS , nerve conduction studies; NHP , natural health product; NPN , natural product number; OGTT , oral glucose tolerance test; TCM , traditional Chinese medicine; TG , triglycerides, UAE , urinary albumin excretion.
Other Relevant Guidelines Physical Activity and Diabetes, p. Author Disclosures Dr. References National Center for Complementary and Integrative Health.
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The two main forms of β-cell replacement therapy are whole-pancreas transplantation or islet cell transplantation. β-Cell replacement therapy can be combined with kidney transplantation if the individual has end-stage renal disease, which may be performed simultaneously or after kidney transplantation.
All decisions about transplantation must balance the surgical risk, metabolic need, and the choice of the individual with diabetes. GFR, glomerular filtration rate. Consider the effects on cardiovascular and renal comorbidities, efficacy, hypoglycemia risk, impact on weight, cost and access, risk for side effects, and patient preferences Table 9.
Indication of overbasalization should prompt reevaluation to further individualize therapy. First-line therapy depends on comorbidities, patient-centered treatment factors, and management needs but will generally include metformin and comprehensive lifestyle modification.
Pharmacotherapy should be started at the time type 2 diabetes is diagnosed unless there are contraindications; for many patients this will be metformin monotherapy in combination with lifestyle modifications.
Metformin is effective and safe, is inexpensive, and may reduce risk of cardiovascular events and death Metformin is available in an immediate-release form for twice-daily dosing or as an extended-release form that can be given once daily. Compared with sulfonylureas, metformin as first-line therapy has beneficial effects on A1C, weight, and cardiovascular mortality 46 ; there is little systematic data available for other oral agents as initial therapy of type 2 diabetes.
Pharmacologic treatment of hyperglycemia in adults with type 2 diabetes. For appropriate context, see Fig. The ADA PPC adaptation emphasizes incorporation of therapy rather than sequential add-on, which may require adjustment of current therapies.
Therapeutic regimen should be tailored to comorbidities, patient-centered treatment factors, and management needs. ASCVD, atherosclerotic cardiovascular disease; CKD, chronic kidney disease; CVD, cardiovascular disease; CVOTs, cardiovascular outcomes trials; DPP-4i, dipeptidyl peptidase 4 inhibitor; eGFR, estimated glomerular filtration rate; GLP-1 RA, glucagon-like peptide 1 receptor agonist; HF, heart failure; SGLT2i, sodium—glucose cotransporter 2 inhibitor; SU, sulfonylurea; T2D, type 2 diabetes; TZD, thiazolidinedione.
The principal side effects of metformin are gastrointestinal intolerance due to bloating, abdominal discomfort, and diarrhea; these can be mitigated by gradual dose titration.
The drug is cleared by renal filtration, and very high circulating levels e. A randomized trial confirmed previous observations that metformin use is associated with vitamin B12 deficiency and worsening of symptoms of neuropathy This is compatible with a report from the Diabetes Prevention Program Outcomes Study DPPOS suggesting periodic testing of vitamin B12 In patients with contraindications or intolerance to metformin, initial therapy should be based on patient factors; consider a drug from another class depicted in Fig.
Insulin has the advantage of being effective where other agents are not and should be considered as part of any combination regimen when hyperglycemia is severe, especially if catabolic features weight loss, hypertriglyceridemia, ketosis are present. However, there is evidence that patients with uncontrolled hyperglycemia associated with type 2 diabetes can also be effectively treated with a sulfonylurea Intensifying to injectable therapies in type 2 diabetes.
DSMES, diabetes self-management education and support; FPG, fasting plasma glucose; GLP-1 RA, glucagon-like peptide 1 receptor agonist; max, maximum; PPG, postprandial glucose. Adapted from Davies et al. Because type 2 diabetes is a progressive disease in many patients, maintenance of glycemic targets with monotherapy is often possible for only a few years, after which combination therapy is necessary.
Traditional recommendations have been to use stepwise addition of medications to metformin to maintain A1C at target. The advantage of this is to provide a clear assessment of the positive and negative effects of new drugs and reduce potential side effects and expense However, there are data to support initial combination therapy for more rapid attainment of glycemic goals 53 , 54 and later combination therapy for longer durability of glycemic effect The VERIFY Vildagliptin Efficacy in combination with metfoRmIn For earlY treatment of type 2 diabetes trial demonstrated that initial combination therapy is superior to sequential addition of medications for extending primary and secondary failure In the VERIFY trial, participants receiving the initial combination of metformin and the dipeptidyl peptidase 4 DPP-4 inhibitor vildagliptin had a slower decline of glycemic control compared with metformin alone and with vildagliptin added sequentially to metformin.
These results have not been generalized to oral agents other than vildagliptin, but they suggest that more intensive early treatment has some benefits and should be considered through a shared decision-making process with patients, as appropriate.
Initial combination therapy should be considered in patients presenting with A1C levels 1. Thus, treatment intensification may not necessarily follow a pure sequential addition of therapy but instead reflect a tailoring of the regimen in alignment with patient-centered treatment goals Fig.
Recommendations for treatment intensification for patients not meeting treatment goals should not be delayed. Shared decision-making is important in discussions regarding treatment intensification. The choice of medication added to initial therapy is based on the clinical characteristics of the patient and their preferences.
Important clinical characteristics include the presence of established ASCVD or indicators of high ASCVD risk, HF, CKD, other comorbidities, and risk for specific adverse drug effects, as well as safety, tolerability, and cost.
A comparative effectiveness meta-analysis suggests that each new class of noninsulin agents added to initial therapy with metformin generally lowers A1C approximately 0. ASCVD, atherosclerotic cardiovascular disease; CV, cardiovascular; CVOT, cardiovascular outcomes trial; DPP-4, dipeptidyl peptidase 4; DKA, diabetic ketoacidosis; DKD, diabetic kidney disease; eGFR, estimated glomerular filtration rate; GI, gastrointestinal; GLP-1 RAs, glucagon-like peptide 1 receptor agonists; HF, heart failure; NASH, nonalcoholic steatohepatitis; SGLT2, sodium—glucose cotransporter 2; SQ, subcutaneous; T2D, type 2 diabetes.
For patients without established ASCVD, indicators of high ASCVD risk, HF, or CKD, the choice of a second agent to add to metformin is not yet guided by empiric evidence comparing across multiple classes. Rather, drug choice is based on efficacy, avoidance of side effects particularly hypoglycemia and weight gain , cost, and patient preferences Similar considerations are applied in patients who require a third agent to achieve glycemic goals.
A recent systematic review and network meta-analysis suggests greatest reductions in A1C level with insulin regimens and specific GLP-1 RAs added to metformin-based background therapy In all cases, treatment regimens need to be continuously reviewed for efficacy, side effects, and patient burden Table 9.
In some instances, patients will require medication reduction or discontinuation. Common reasons for this include ineffectiveness, intolerable side effects, expense, or a change in glycemic goals e. The need for the greater potency of injectable medications is common, particularly in people with a longer duration of diabetes.
The addition of basal insulin, either human NPH or one of the long-acting insulin analogs, to oral agent regimens is a well-established approach that is effective for many patients. In addition, recent evidence supports the utility of GLP-1 RAs in patients not at glycemic goal. While most GLP-1 RAs are injectable, an oral formulation of semaglutide is now commercially available In trials comparing the addition of an injectable GLP-1 RA or insulin in patients needing further glucose lowering, glycemic efficacy of injectable GLP-1 RA was similar or greater than that of basal insulin 62 — GLP-1 RAs in these trials had a lower risk of hypoglycemia and beneficial effects on body weight compared with insulin, albeit with greater gastrointestinal side effects.
Thus, trial results support GLP-1 RAs as the preferred option for patients requiring the potency of an injectable therapy for glucose control Fig. In patients who are intensified to insulin therapy, combination therapy with a GLP-1 RA has been shown to have greater efficacy and durability of glycemic treatment effect than treatment intensification with insulin alone.
However, cost and tolerability issues are important considerations in GLP-1 RA use. Costs for diabetes medications has increased dramatically over the past two decades, and an increasing proportion is now passed on to patients and their families Table 9.
Of note, prices listed are average wholesale prices AWP 70 and National Average Drug Acquisition Costs NADAC 71 , separate measures to allow for a comparison of drug prices, but do not account for discounts, rebates, or other price adjustments often involved in prescription sales that affect the actual cost incurred by the patient.
Medication costs can be a major source of stress for patients with diabetes and contribute to worse adherence to medications 72 ; cost-reducing strategies may improve adherence in some cases Median monthly day AWP and NADAC of maximum approved daily dose of noninsulin glucose-lowering agents in the U.
Utilized to calculate median AWP and NADAC min, max ; generic prices used, if available commercially. Thus, a practical extension of these results to clinical practice is to use these drugs preferentially in patients with type 2 diabetes and established ASCVD or indicators of high ASCVD risk.
Emerging data suggest that use of both classes of drugs will provide additional cardiovascular and kidney outcomes benefit; thus, combination therapy with an SGLT2 inhibitor and a GLP-1 RA may be considered to provide the complementary outcomes benefits associated with these classes of medication In cardiovascular outcomes trials, empagliflozin, canagliflozin, dapagliflozin, liraglutide, semaglutide, and dulaglutide all had beneficial effects on indices of CKD, while dedicated renal outcomes studies have demonstrated benefit of specific SGLT2 inhibitors.
Additional large randomized trials of other agents in these classes are ongoing. Many patients with type 2 diabetes eventually require and benefit from insulin therapy Fig. See the section insulin injection technique , above, for guidance on how to administer insulin safely and effectively.
The progressive nature of type 2 diabetes should be regularly and objectively explained to patients, and clinicians should avoid using insulin as a threat or describing it as a sign of personal failure or punishment.
Rather, the utility and importance of insulin to maintain glycemic control once progression of the disease overcomes the effect of other agents should be emphasized. Educating and involving patients in insulin management is beneficial.
For example, instruction of patients in self-titration of insulin doses based on glucose monitoring improves glycemic control in patients with type 2 diabetes initiating insulin Comprehensive education regarding self-monitoring of blood glucose, diet, and the avoidance and appropriate treatment of hypoglycemia are critically important in any patient using insulin.
Basal insulin alone is the most convenient initial insulin regimen and can be added to metformin and other oral agents.
Starting doses can be estimated based on body weight 0. The principal action of basal insulin is to restrain hepatic glucose production and limit hyperglycemia overnight and between meals 76 , Control of fasting glucose can be achieved with human NPH insulin or a long-acting insulin analog.
In clinical trials, long-acting basal analogs U glargine or detemir have been demonstrated to reduce the risk of symptomatic and nocturnal hypoglycemia compared with NPH insulin 78 — 83 , although these advantages are modest and may not persist Longer-acting basal analogs U glargine or degludec may convey a lower hypoglycemia risk compared with U glargine when used in combination with oral agents 85 — Clinicians should be aware of the potential for overbasalization with insulin therapy.
Indication of overbasalization should prompt reevaluation to further individualize therapy The cost of insulin has been rising steadily over the past two decades, at a pace several fold that of other medical expenditures Therefore, consideration of cost is an important component of effective management.
For many individuals with type 2 diabetes e. Additionally, approval of follow-on biologics for insulin glargine, the first interchangeable insulin glargine product, and generic versions of analog insulins may expand cost-effective options.
Median cost of insulin products in the U. AWP or NADAC calculated as in Table 9. Many individuals with type 2 diabetes require doses of insulin before meals, in addition to basal insulin, to reach glycemic targets. The prandial insulin regimen can then be intensified based on individual needs see Fig.
Titration can be based on home glucose monitoring or A1C. With significant additions to the prandial insulin dose, particularly with the evening meal, consideration should be given to decreasing basal insulin.
Meta-analyses of trials comparing rapid-acting insulin analogs with human regular insulin in with type 2 diabetes have not reported important differences in A1C or hypoglycemia 96 , Several concentrated insulin preparations are currently available.
U regular insulin is, by definition, five times more concentrated than U regular insulin. U regular insulin has distinct pharmacokinetics with delayed onset and longer duration of action, has characteristics more like an intermediate-acting NPH insulin, and can be used as two or three daily injections U glargine and U degludec are three and two times as concentrated as their U formulations, respectively, and allow higher doses of basal insulin administration per volume used.
U glargine has a longer duration of action than U glargine but modestly lower efficacy per unit administered 99 , These concentrated preparations may be more convenient and comfortable for individuals to inject and may improve adherence in those with insulin resistance who require large doses of insulin.
While U regular insulin is available in both prefilled pens and vials, other concentrated insulins are available only in prefilled pens to minimize the risk of dosing errors. Inhaled insulin is available as a rapid-acting insulin; studies in individuals with type 1 diabetes suggest rapid pharmacokinetics 8.
A pilot study found evidence that compared with injectable rapid-acting insulin, supplemental doses of inhaled insulin taken based on postprandial glucose levels may improve blood glucose management without additional hypoglycemia or weight gain , although results from a larger study are needed for confirmation.
Use of inhaled insulin may result in a decline in lung function reduced forced expiratory volume in 1 s [FEV 1 ]. Inhaled insulin is contraindicated in individuals with chronic lung disease, such as asthma and chronic obstructive pulmonary disease, and is not recommended in individuals who smoke or who recently stopped smoking.
All individuals require spirometry FEV 1 testing to identify potential lung disease prior to and after starting inhaled insulin therapy.
This approach can use a GLP-1 RA added to basal insulin or multiple doses of insulin. The combination of basal insulin and GLP-1 RA has potent glucose-lowering actions and less weight gain and hypoglycemia compared with intensified insulin regimens — The DUAL VIII randomized controlled trial demonstrated greater durability of glycemic treatment effect with the combination GLP-1 RA—insulin therapy compared with addition of basal insulin alone In select individuals, complex insulin regimens can also be simplified with combination GLP-1 RA—insulin therapy in type 2 diabetes Two different once-daily, fixed dual-combination products containing basal insulin plus a GLP-1 RA are available: insulin glargine plus lixisenatide iGlarLixi and insulin degludec plus liraglutide IDegLira.
Intensification of insulin treatment can be done by adding doses of prandial insulin to basal insulin. Starting with a single prandial dose with the largest meal of the day is simple and effective, and it can be advanced to a regimen with multiple prandial doses if necessary Alternatively, in an individual on basal insulin in whom additional prandial coverage is desired, the regimen can be converted to two doses of a premixed insulin.
Each approach has advantages and disadvantages. On the other hand, two doses of premixed insulin is a simple, convenient means of spreading insulin across the day.
Figure 9. When initiating combination injectable therapy, metformin therapy should be maintained, while sulfonylureas and DPP-4 inhibitors are typically weaned or discontinued. In individuals with suboptimal blood glucose control, especially those requiring large insulin doses, adjunctive use of a thiazolidinedione or an SGLT2 inhibitor may help to improve control and reduce the amount of insulin needed, though potential side effects should be considered.
The ADA Professional Practice Committee focused on several key areas in Fig. Areas of discussion and updated changes are outlined below. Title and Purpose of Algorithm. Given the significant impact the cardiovascular outcomes trials have had on understanding the management of type 2 diabetes and the different guidelines and algorithms being proposed by different societies, it was important to identify the purpose of Fig.
The purpose of this guidance is to support achievement of glycemic goals to reduce long-term complications, highlighting aspects of therapy that support patient-centered goals. Initial Therapy. First-line therapy for the treatment of hyperglycemia has traditionally been metformin and comprehensive lifestyle.
Recognizing the multiple treatment goals and comorbidities for individuals with type 2 diabetes, alternative initial treatment approaches to metformin are acceptable, depending on comorbidities, patient-centered treatment factors, and glycemic and comorbidity management needs.
This pathway has been streamlined to highlight therapies that have evidence to support cardiovascular risk reduction and glycemic management, prioritizing GLP-1 RAs and SGLT2 inhibitors for this population.
This pathway highlights the emerging evidence of improvement in cardiovascular outcomes with SGLT2 inhibitors in individuals with type 2 diabetes and existing HF. This pathway has been updated based on populations studied in renal and cardiovascular outcomes studies and to specify recommendations when further intensification is required e.
Principle of Incorporation. Prior algorithms have conveyed sequential addition of therapy. Not all treatment intensification results in sequential add-on therapy, but in some cases it may involve switching therapy or weaning current therapy to accommodate therapeutic changes.
For example, discontinuation of the DPP-4 inhibitor is recommended when intensifying from a DPP-4 inhibitor to a GLP-1 RA, given overlapping mechanisms. In addition, when cardioprotective agents e. Treatment Intensification. For the individual with high risk or established ASCVD, CKD, or HF whose A1C remains above target, further treatment intensification should be based on comorbidities, patient-centered treatment factors, and management needs as highlighted on the right side of Fig.
Agents should be considered that provide adequate efficacy to achieve and maintain glycemic goals Table 9. Minimize Hypoglycemia. Agents with good efficacy for weight loss are preferred , with incorporation of additional agents as indicated.
Access and cost are universal considerations. Classes with medications currently available in generic form are listed. Suggested citation: American Diabetes Association Professional Practice Committee.
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View large Download slide. Timing and distribution. Adjusting doses. Can adjust basal rates for varying insulin sensitivity by time of day, for exercise and for sick days. Flexibility in meal timing and content.
Pump can deliver insulin in increments of fractions of units. Potential for integration with CGM for low-glucose suspend or hybrid closed-loop. Most expensive regimen. Must continuously wear one or more devices.
Risk of rapid development of ketosis or DKA with interruption of insulin delivery. Potential reactions to adhesives and site infections. Most technically complex approach harder for people with lower numeracy or literacy skills. Mealtime insulin: if carbohydrate counting is accurate, change ICR if glucose after meal consistently out of target.
Can use pens for all components. Insulin analogs cause less hypoglycemia than human insulins. At least four daily injections. Most costly insulins. Smallest increment of insulin is 1 unit 0. LAAs may not cover strong dawn phenomenon rise in glucose in early morning hours as well as pump therapy.
LAA: based on overnight or fasting glucose or daytime glucose outside of activity time course, or URAA or RAA injections. May be feasible if unable to carbohydrate count. All meals have RAA coverage.
N less expensive than LAAs. Shorter duration RAA may lead to basal deficit during day; may need twice-daily N. Greater risk of nocturnal hypoglycemia with N. Requires relatively consistent mealtimes and carbohydrate intake.
Pre-breakfast RAA: based on BGM after breakfast or before lunch. Pre-lunch RAA: based on BGM after lunch or before dinner.
Pre-dinner RAA: based on BGM after dinner or at bedtime. Evening N: based on fasting or overnight BGM. R can be dosed based on ICR and correction. All meals have R coverage. Least expensive insulins. Greater risk of delayed post-meal hypoglycemia with R.
Diabetes is a Diabetes and alternative treatment approaches disorder alternativ the endocrine system. Traveling and eating for sports events is becoming a severe threat to worldwide health. According to a report by the National Diabetes Alternatkve, 7. populationand 8. A report by the Indian Diabetes Federation also showcases surprising numbers, estimating a total of about 90 million diabetes patients by There are multiple medications and medical interventions available to manage and treat diabetes, but there is no report on total recovery from diabetes up to this date. Top Diabetees Alternative Diabetes Therapies: Are Patients Undermining Their Alternativf By Judith C. Thalheimer, Diabetes and alternative treatment approaches, LDN Today's Geriatric Medicine Vol. Approaces with diabetes are turning to unregulated and understudied supplements, foods, and other alternative treatments. Although some may prove useful, others carry risk of real harm. Many individuals with diabetes are turning to home remedies and alternative treatments in an attempt to mitigate their chronic illness or prevent complications.
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