Need Help

[pguererro]

In the past I’ve heard members of this board reference past studies and data that supports using Bolus insulin early in Type 2 patients. If anyone could point me to this data it would be greatly appreciated. Thanks

[peppy]

Jul 10, 2018 6:16:42 GMT -5 pguererro said:

In the past I’ve heard members of this board reference past studies and data that supports using Bolus insulin early in Type 2 patients. If anyone could point me to this data it would be greatly appreciated. Thanks

Early Short-term Intensive Insulin Causes the Remission of Type 2 Diabetes
September 10th, 2016

Source: www.diabetesincontrol.com/early-short-term-intensive-insulin-causes-the-remission-of-type-2-diabetes/

Excerpts:

In early type 2 diabetes (T2DM), short-term intensive insulin therapy (IIT) for 2-4 weeks can decrease insulin resistance, reduce glucagonemia, improve β-cell function, and even induce a remission of diabetes that can last up to one year in some patients.

Data was evaluated from the placebo arm of a double-blind randomized controlled trial in which patients with early T2DM (≤7 years duration) underwent 4 weeks of IIT (basal detemir, bolus aspart), followed by placebo therapy for 48 weeks (n=25). Participants underwent an oral glucose tolerance test every 12 weeks, enabling serial assessment of insulin sensitivity, α-cell response, and β-cell function. Diabetes remission was defined as A1c<6.5% on no medication for T2DM.

For the study design, data from the placebo arm of the double-blind randomized controlled trial in which 25 patients within 7 y of T2D diagnosis received 4 weeks of intensive basal/bolus insulin therapy followed by placebo for 48 wk. An oral glucose tolerance test (OGTT) every 12 weeks used to assess insulin sensitivity and beta-cell function. Then diabetes remission was defined as HbA1c <6.5% with no T2D medications.

The results showed that at 48 weeks after stopping intensive insulin, 14 participants (56%) were in diabetes remission. At baseline, the remission group had shorter duration of diabetes (1.2 vs 2.6 y; p=.03), lower A1c (6.2% vs 7.1%, p=.006), and better β-cell function.

The 2 groups did not differ in clinical characteristics such as age, gender, ethnicity, pre-study diabetes treatment, body mass index, waist circumference, blood pressure, liver enzymes, or insulin sensitivity.

Then, in logistic regression analyses, shorter duration of diabetes supplanted baseline A1c (p=.24) and β-cell function (p=.19) as an independent predictor of remission at 48 weeks (OR, 0.22; 95% CI 0.05-0.92; p=.04)

At 48 weeks post-IIT, 56% of the participants remained in remission. Comparison of remitters to non-remitters revealed no differences in waist, body mass index, insulin sensitivity (Matsuda index), or glucagon profile, either at baseline or over 48 weeks. Compared to non-remitters, the remission group had lower baseline A1c (p=0.006) and better baseline β-cell function

The key determinant of the likelihood of inducing sustained drug-free diabetes remission with short-term IIT is early intervention, particularly within the first 2 years after diagnosis. And reversing or delaying type 2 diabetes may help prevent morbidity and reduce healthcare costs.



Read more: mnkd.proboards.com/thread/3407/blood-sugar-101-tell-diabetes#ixzz5Kqo0Ia6l

[pguererro]

Thanks so much peppy!!

[agedhippie]

Just to be clear, all the papers I have seen says basal + bolus, as does that paper.

The other area I would look is the RISE study. It's a big long running trial and they have positive results for early insulin in adults (but not in children).

[mnholdem]

This is another very good meta-analysis study report from 2014 that I quote quite often:

onlinelibrary.wiley.com/doi/full/10.1002/dmrr.2603

Excerpt:

Building on results of this trial and those of six other smaller trials of STII [Short-Term Intensive Insulin] therapy, a meta‐analysis involving 839 participants (including 251 patients randomized to STII therapy in the above study ⁴⁴) was performed and further underscored the robustness of the evidence supporting STII therapy ⁵⁰. In that analysis, 46% of patients remained in drug‐free remission after 12 months. All but one study showed an improvement in beta‐cell function, as assessed by homeostatic model assessment [HOMA]‐B, and all but one study showed a decrease in insulin resistance, as assessed by HOMA‐IR.

In the pooled data, the proportion of patients in drug‐free remission was:

• 66.2% [292/441] at 3 months
• 58.9% [222/377] at 6 months
• 46.3% [229/495] at 12 months
• 42.1% [53/126] at 24 months

These rates of remission are far greater than those that can be achieved with any other currently available medical therapy for diabetes.

---

Current guidelines and STII therapy

Despite these promising results, the use of insulin as a first‐line therapy in newly diagnosed patients with type 2 diabetes remains underutilized as an effective treatment option. One reason for this lack of acceptance is that current treatment guidelines for type 2 diabetes do not adequately address the concept of STII therapy and are generally cautious in their recommendations about when to initiate insulin.

For example, the American Diabetes Association [ADA]/European Association for the Study of Diabetes [EASD] guidelines emphasize progressive intensification of treatment and recommend metformin as the preferred initial therapy for most patients, reserving insulin as a later‐stage therapy or as an option for people with HbA1c ≥10–12% ⁸. In the latter group, the ADA/EASD guidelines do mention that it may be possible to taper off insulin once initial glucotoxicity is reversed and to transfer to other types of antihyperglycaemic medications.

In the American Association of Clinical Endocrinologists 2013 algorithm, insulin is recommended for patients with symptoms and HbA1c ≥9.0% ⁷.

In the International Diabetes Federation Global Guidelines, insulin is listed as a third‐line or fourth‐line therapy ⁵⁴.

Chinese guidelines also list insulin as a third‐line treatment ⁵⁵.

None of these guidelines mention STII therapy, despite a growing body of evidence supporting its use. The Global Partnership for Effective Diabetes Management model recommendations do mention temporary use of insulin for newly diagnosed adults with HbA1c >9% [75 mmol/mol] but do not elaborate further nor strongly endorse the STII therapy concept ⁵⁶.

On the basis of the evidence in the literature and our own clinical experience, we propose that expert panels and diabetes organizations involved in developing and promoting treatment guidelines and algorithms for type 2 diabetes should discuss STII therapy more formally in future revisions and consider listing this therapy as an option for newly diagnosed patients.

[sayhey24]

Jul 10, 2018 6:16:42 GMT -5 pguererro said:

In the past I’ve heard members of this board reference past studies and data that supports using Bolus insulin early in Type 2 patients. If anyone could point me to this data it would be greatly appreciated. Thanks

PG - I think what Aged said is correct.  Most studies were done with a basal and still showed early insulin intervention is the way to go.  Think of what the result would be if properly dosed with afrezza first at all meals?

I believe such a study was done by Mannkind but is part of the lost studies which Dr. Kendall says he is going to release.  The 175 used afrezza with metofrmin but it was only trying to show a minor decrease in A1c and the PWDs were way under-dosed.

The issue is the current ADA step program says use basal before the RAA.  While this is the medically incorrect way to treat the T2 the fear of hypoglycemia with the RAAs is too great.  This plus the fact that some of the studies were done before the RAAs were invented limit the study pool.

What is it you are trying to do?  If its show a PCP afrezza should be used first before the anti-glycemics and even before metformin you will have to wait until ADA2019.  The best stab at that was done by VDex but it may get laughed at by many medical professionals as it is not an "Official Study".  However, what I tell people is try it yourself and see what your results are.  Now with the Libre readily available its easy to do.

static1.squarespace.com/static/5a37ff648fd4d234be3cea06/t/5b3c0de503ce6479dfbfc8ab/1530662387943/vdex-whitepaper-070318.pdf

[pguererro]

Strictly for internal discussion with colleagues